Thermo-thickening compounds for non-polar liquid

ABSTRACT

A bis-urea compound of general formula (IV): 
     
       
         
         
             
             
         
       
     
     The compound is useful as a thermo-thickening agent in a non-polar liquid such as engine lubricating oil or thermosetting varnish. Also, a method for preparing the thermo-thickening compound. Further, a composition comprising the thermo-thickening compound and a non-polar liquid.

FIELD OF INVENTION

The present invention relates to the field of thermo-thickeners. Moreprecisely, the invention relates to bis-urea compounds useful as athermo-thickening agents in non-polar liquids, such as for exampleengine lubricating oils or thermosetting resins. The present inventionalso concerns a method for preparing said thermo-thickening compounds.The present invention also relates to compositions comprising saidthermo-thickening compounds.

BACKGROUND OF INVENTION

As a general rule, the viscosity of a fluid decreases when temperatureincreases. However, for some applications, being able to avoid suchdecrease of viscosity is essential. Thus, using additives able tocompensate this effect is necessary in such cases. In aqueous medium,numerous solutions exist. However, this is not the case in organicmedium.

For example, in the engine lubricating field, an efficient lubricatingoil has to avoid (i) metal engine surfaces rubbing together and wearout, and (ii) the agglomeration of deposits by maintaining them insuspension. If the viscosity is too high at low temperatures, the oilcannot flow into the engine. Besides, if the viscosity is too low whenthe engine is hot, the oil cannot ensure efficient mechanical propertiesand may disrupt the engine operation.

Therefore, one of the essential requirement for a lubricating oil isthat at low temperatures, it has a low viscosity to assist in coldstarting, while at higher temperatures, its viscosity should bemaintained for keeping efficient mechanical properties.

Today, very few suitable solutions are available in the market forallowing enhancing the rheological properties of non-polar media (suchas fuel, engine lubricating oil, etc . . . ) having constraints as thosementioned above.

Thus, there is a need for providing thermo-thickening agents suitablefor non-polar liquids. By “thermo-thickening” it is herein referred tothe ability to counteract the natural decrease of viscosity of a liquidupon temperature rise.

Surprisingly, the Applicant herein evidences that bis-urea compounds maybe used as efficient thermo-thickening agents.

Bis-urea have already been disclosed for various applications; inparticular as organogelling agent. For instance, WO2014/096323 disclosesthe use of bis-urea compounds for providing gelled hydrocarbon-basedfuel composition at room temperature. In WO2014/096323, the viscosity ofthe gelled fuel decreases when a shear stress is applied to said gel.WO2014/096323 does not disclose nor suggest that bis-urea compoundsdisclosed therein may be able to maintain or increase the viscosity of anon-polar solution, upon heating.

Advantageously, the compounds of the invention are easily solubilized ina liquid; especially, in a non-polar liquid. Advantageously, thecompounds of the invention do not lead to deposits. Advantageously, thecompounds of the invention are easily tunable. Advantageously, thecompounds of the invention are enantiopure compounds.

SUMMARY

This invention thus relates to the use as thermo-thickening agent of acompound of general formula (IV):

-   -   wherein:    -   R_(a), R_(b), R_(c) and R_(d) are each independently selected        from H, alkyl, heteroalkyl, alkoxy, amino, alkylamino and halo;        preferably R_(b) and R_(d) are each independently selected from        H, C₁-C₄ alkyl, C₁-C₄ heteroalkyl, C₁-C₄ alkoxy, C₁-C₄        dialkylamino and halo; more preferably R_(b) and R_(d) are each        independently selected from at least one C₁-C₄ alkyl or halo;    -   R₁′ and R₂′ are each independently selected from linear alkyl,        heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl and        macromolecular groups, optionally substituted by one or more        halo; preferably R₁′ and R₂′ are each independently selected        from linear alkyl or linear heteroalkyl group, said linear group        being optionally substituted by one or more halo; more        preferably R₁′ and R₂′ are each independently selected from        linear C₆-C₁₈ alkyl or heteroalkyl group, said linear group        being optionally substituted by one or more terminal halo;    -   R₃′, R₃, R₄, R₄′ R₅′, R₅, R₆ and R₆′ are each independently        selected from H, alkyl, alkenyl, aryl, heteroalkyl,        heteroalkenyl, heteroaryl, alkylaryl, arylalkyl, heteroarylalkyl        or alkylheteroaryl, optionally substituted by guanidine, aryl,        pyrrolidine, imidazole, hydroxyaryl, carboxy, selanyl, hydroxyl,        amide, thiol, alkylthio, amino, deuterium or halo; preferably        R₃′, R₃, R₄, R₄′ R₅′, R₅, R₆ and R₆′ are each independently        selected from H, C₁-C₁₂ alkyl substituted by at least one aryl,        said aryl being optionally substituted by one or more halo or        deuterium;    -   Z₁ and Z₁′ are each independently selected from O and S atoms;    -   Z₂ and Z₂′ are each independently selected from —NH—, O and S        atoms;    -   n represents a positive integer from 0 to 10; preferably n is        equal to 0; and    -   optionally, * stands for a stereogenic center;    -   provided that R₁′ and R₂′ does not represent both a methyl        group.

According to one embodiment, the compound is of general formula (IVbis):

-   -   wherein R_(a), R_(b), R_(c), R_(d), R₁′, R₂′, R₃, R₃′, R₄, R₄′,        Z₁, Z₁′, Z₂ and Z₂′ are as defined in formula (IV).    -   According to one embodiment, the compound of formula (IVbis),        R_(a) and R_(c) are both H.    -   According to one embodiment, the thermo-thickening agent is used        for a non-polar liquid; preferably the non-polar liquid is        selected from an oil, a grease, a monomer, a thermosetting        resin, a perfume or a fuel.    -   According to one embodiment, the thermo-thickening is performed        at a temperature ranging from 5° C. to 100° C.; preferably from        10° C. to 60° C.; more preferably from 20° C. to 50° C.    -   According to one embodiment, the invention refers to the use as        thermo-thickening agent of a compound of general formula (IV)        for further improving the cold flow property of a non-polar        liquid.    -   The present invention also refers to a compound of general        formula (IV):

-   -   wherein:    -   R_(a), R_(b), R_(c) and R_(d) are each independently selected        from H, alkyl, heteroalkyl, alkoxy, amino, alkylamino and halo;        preferably R_(b) and R_(d) are each independently selected from        H, C₁-C₄ alkyl, C₁-C₄ heteroalkyl, C₁-C₄ alkoxy, C₁-C₄        dialkylamino and halo; more preferably R_(b) and R_(d) are each        independently selected from at least one C₁-C₄ alkyl or halo;    -   R₁′ and R₂′ are each independently selected from linear alkyl,        heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl and        macromolecular groups, optionally substituted by one or more        halo; preferably R₁′ and R₂′ are each independently selected        from linear alkyl or linear heteroalkyl group, said linear group        being optionally substituted by one or more halo; more        preferably R₁′ and R₂′ are each independently selected from        linear C₆-C₁₈ alkyl or heteroalkyl group, said linear group        being optionally substituted by one or more terminal halo;    -   R₃′, R₃, R₄, R₄′ R₅′, R₅, R₆ and R₆′ are each independently        selected from H, alkyl, alkenyl, aryl, heteroalkyl,        heteroalkenyl, heteroaryl, alkylaryl, arylalkyl, heteroarylalkyl        or alkylheteroaryl, optionally substituted by guanidine, aryl,        pyrrolidine, imidazole, hydroxyaryl, carboxy, selanyl, hydroxyl,        amide, thiol, alkylthio, amino, deuterium or halo; preferably        R₃′, R₃, R₄, R₄′ R₅′, R₅, R₆ and R₆′ are each independently        selected from H, C₁-C₁₂ alkyl substituted by at least one aryl,        said aryl being optionally substituted by one or more halo or        deuterium;    -   Z₁ and Z₁′ are each independently selected from O and S atoms;    -   Z₂ and Z₂′ are each independently selected from —NH—, O and S        atoms;    -   n represents a positive integer from 0 to 10; preferably n is        equal to 0; and    -   optionally, * stands for a stereogenic center;    -   provided that R₁′ and R₂′ does not represent both a methyl        group.    -   According to one embodiment, n is equal to 0 (i.e. compounds        having formula (IV bis)).    -   According to one embodiment, Z₁, Z₁′, Z₂ and Z₂′ represent O        atoms.    -   According to one embodiment, the compound is selected from:        -   (2S,2′S)-dihexyl            2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-diheptyl            2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-dioctyl            2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-dioctyl            2,2′-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-dioctyl            2,2′-((((4,6-dichloro-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-dinonyl            2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-dinonyl            2,2′-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-didecyl            2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-diundecyl            2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-didodecyl            2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-didodecyl            2,2′-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-ditridecyl            2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-ditetradecyl            2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-dihexadecyl            2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-dihexadecyl            2,2′-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-dioctadecyl            2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-dioctyl            2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-pentadeuteriumphenylpropanoate);        -   (2S,2′S)-bis(12,12,12-tribromododecyl)            2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-bis(12,12,12-tribromododecyl)            2,2′-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);        -   (2S,2′S)-bis(12,12,12-tribromododecyl)            2,2′-((((4,6-dichloro-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);            and        -   (2S,2′S)-bis(12,12,12-trichlorododecyl)            2,2′-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate).    -   The present invention also refers to a composition comprising at        least one compound of the invention, and a non-polar liquid.    -   According to one embodiment, the liquid is selected from an oil        (or lubricant), a grease, a monomer, a thermosetting resin, a        perfume or a fuel.    -   According to one embodiment, the compound is at a concentration        ranging from more than 0 to 5% by weight to the total weight of        the composition; preferably from 0.1 to 1% by weight to the        total weight of the composition.    -   The present invention also refers to a process for manufacturing        a compound of formula (IV bis), comprising reacting at least one        ester ammonium salt of formula (A-1):

-   -   wherein    -   R₃′ and R₃ are each independently selected from H, alkyl,        alkenyl, aryl, heteroalkyl, heteroalkenyl, heteroaryl,        alkylaryl, arylalkyl, heteroarylalkyl or alkylheteroaryl,        optionally substituted by guanidine, aryl, pyrrolidine,        imidazole, hydroxyaryl, carboxy, selanyl, hydroxyl, amide,        thiol, alkylthio, amino, deuterium or halo;    -   R₁′ is each independently selected from linear alkyl,        heteroalkyl, alkenyl, heteroalkenyl, alkynyl and heteroalkynyl        group, optionally substituted by one or more halo; and    -   X⁻ is an anion, preferably selected from chloride, bromide,        sulfate, hydrogenosulfate and sulfonate; more preferably X⁻ is        tosylate.    -   with        -   (a) either a diisocyanate of general formula (A-2bis):

-   -   -   wherein R_(a), R_(b), R_(c) and R_(d) are each independently            selected from H, alkyl, heteroalkyl, alkoxy, amino,            alkylamino and halo; preferably R_(b) and R_(d) are each            independently selected from H, C₁-C₄ alkyl, C₁-C₄            heteroalkyl, C₁-C₄ alkoxy, C₁-C₄ dialkylamino and halo; more            preferably R_(b) and R_(d) are each independently selected            from at least one C₁-C₄ alkyl or halo;        -   (b) or a mixture of reagents allowing the in situ            preparation of diisocyanate of formula (A-2bis), preferably            a mixture of a compound having a carbonyl function such as            bis(trichloromethyl)carbonate or phosgene, and a diamine of            formula (A-3bis):

-   -   -   wherein R_(a), R_(b), R_(c) and R_(d) are defined above.

    -   According to one embodiment, the process of the invention        further comprises a preliminary step of preparing ester ammonium        salt of formula (A-1) by reacting an amino acid and an alcohol        such as hydroxyalkane.

Definitions

In the present invention, the following terms have the followingmeanings:

-   -   “Thermo-thickening agent”: refers to any chemical compound able,        when added into a liquid (1) to increase the viscosity of said        liquid at room temperature compared to the viscosity of said        liquid free of any thermo-thickening agent; and (2) to avoid        that, upon temperature rise, the viscosity of said liquid        decreases to the same extend than it decreases in absence of any        thermo-thickening agent. In a preferred embodiment, as        illustrated on FIG. 1, if in absence of the thermo-thickening        agent the viscosity of a liquid decreases of x, from μ_(liq−1)        to μ_(lid−2), upon temperature rise from T₁ to T₂ (dotted line);        then the addition of the thermo-thickening agent of the        invention enables that the decrease of viscosity of the        resulting solution upon temperature rise from T₁ to T₂ to be of        less than x/2, from μ_(sol−1) to μ_(sol−2a) (solid lines). In        one embodiment, in presence of the thermo-thickening agent, the        decrease of viscosity is less than x/2 (solid line (a)). In a        preferred embodiment, in presence of the thermo-thickening        agent, the viscosity is maintained in a narrow range around the        viscosity of the solution at T₁ (solid line (b)). In another        specific embodiment, in presence of the thermo-thickening agent,        the viscosity is increased above the viscosity of the solution        at T₁ (solid line (c));    -   “Thermosetting resin”: refers to a chemical compound in a        viscous liquid that after curing induced by the action of heat        or suitable radiation, changes irreversibly into an infusible        and insoluble polymer network;    -   “Aryl”: refers to a polyunsaturated, aromatic hydrocarbyl group        having a single ring or multiple aromatic rings fused together        (such as naphtyl) or linked covalently, typically containing 5        to 20, and preferably 6 to 12, carbon atoms having one or more        aromatic rings among which it is possible to cite the phenyl        group, the biphenyl group, the 1-naphthyl group, the 2-naphthyl        group, the tetrahydronaphthyl group, the indanyl group and the        binaphthyl group. In the present invention, the term “aryl”        preferably refers to a single ring;    -   “Alkenyl”: refers to a linear or branched hydrocarbon chain        having at least one double bond, preferably linear hydrocarbon        chain having at least one double bond. According to one        embodiment, alkenyl refers to a C₆-C₁₈ alkenyl, preferably a        linear C₆-C₁₈ alkenyl chain. According to one embodiment,        alkenyl refers to a C₈, C₉, C₁₀, C₁₁, C₁₂, C₁₃, C₁₄, C₁₅ or C₁₆        alkenyl, preferably a linear C₈, C₉, C₁₀, C₁₁, C₁₂, C₁₃, C₁₄,        C₁₅ or C₁₆ alkenyl chain;    -   “Alkynyl”: refers to a linear or branched hydrocarbon chain        having at least one triple bond, preferably linear hydrocarbon        chain having at least one triple bond. According to one        embodiment, alkynyl refers to a C₆-C₁₈ alkynyl, preferably a        linear C₆-C₁₈ alkynyl chain. According to one embodiment,        alkynyl refers to a C₈, C₉, C₁₀, C₁₁, C₁₂, C₁₃, C₁₄, C₁₅ or C₁₆        alkynyl, preferably a linear C₈, C₉, C₁₀, C₁₁, C₁₂, C₁₃, C₁₄,        C₁₅ or C₁₆ alkynyl chain;    -   “Alkyl”: refers to a hydrocarbyl radical of formula        C_(n)H_(2n+1) wherein n is a number greater than or equal to 1.        Generally, alkyl groups of this invention comprise from 1 to 20        carbon atoms. Alkyl groups may be linear or branched and may be        substituted as indicated herein. When a subscript is used herein        following a carbon atom, the subscript refers to the number of        carbon atoms that the named group may contain. Thus, for        example, C₁-C₄ alkyl means an alkyl of one to four carbon atoms.        C₁-C₂₀ alkyl includes all linear, or branched alkyl groups with        between 1 and 20 carbon atoms, and thus includes methyl, ethyl,        n-propyl, i-propyl, butyl and its isomers (e.g. n-butyl, i-butyl        and t-butyl); pentyl and its isomers, hexyl and its isomers,        heptyl and its isomers, octyl and its isomers, nonyl and its        isomers, decyl and its isomers, undecyl and its isomers, dodecyl        and its isomers, tridecyl and its isomers, tetradecyl and its        isomers, pentadecyl and its isomers, hexadecyl and its isomers,        heptadecyl and its isomers, octodecyl and its isomers, nonadecyl        and its isomers, eicosyl and its isomers. According to one        embodiment, alkyl refers to a linear hydrocarbyl radical of        formula C_(n)H_(2n+1) wherein n is a number greater than or        equal to 1. According to one embodiment, alkyl refers to a        C₆-C1₈ alkyl, preferably a linear C₆-C1₈ alkyl chain. According        to one embodiment, alkyl refers to a C₈, C₉, C₁₀, C₁₁, C₁₂, C₁₃,        C₁₄, C₁₅ or C₁₆ alkyl, preferably a linear C₈, C₉, C₁₀, C₁₁,        C₁₂, C₁₃, C₁₄, C₁₅ or C₁₆ alkyl chain;    -   “Alkylaryl”: refers to an aryl group substituted by an alkyl        group, which may be represented as alkyl-aryl-;    -   “Alkylheteroaryl”: refers to a heteroaryl group substituted by        an alkyl group, which may be represented as alkyl-heteroaryl-;    -   “Alkoxy”: refers to any —O-alkyl or —O-aryl group;    -   “Amide”: refers to the moieties —CO—NRR′ or —NR—CO—R′, wherein R        and R′ represent preferably H, alkyl or aryl. According to a        specific embodiment, “amide” refers to the —CO—NH₂ moiety;    -   “Amino”: refers to any compound derived from ammoniac NH₃ by        substitution of one or more hydrogen atoms with an organic        radical. Amino preferably refers to —NH₂, —NHR and —NRR′ wherein        R and R′ are preferably alkyl groups. Therefore “amino” includes        alkylamino groups: monoalkylamino and dialkylamino;    -   “Arylalkyl”: refers to an alkyl group substituted by an aryl        group, which may be represented as aryl-alkyl-;    -   “Carboxy”: refers to —COOH;    -   “Cold flow property”: refers to ability for a fluid or        semi-fluid to flow at a temperature equal or lower to room        temperature (i.e. about 25° C.);    -   “Fuel”: refers to any product for supplying energy to a heat        engine;    -   “Grease”: refers to any product under the form of a semifluid to        solid product obtained by dispersing a thickening or gelling        agent in an oil (or lubricant);    -   “Halo”: refers to halogen atom selected from fluoro (—F), chloro        (—Cl), bromo (—Br) and iodo (—I) atoms. In the present        invention, the terms “terminal halo” refer to one or more halo        atoms linked to a terminal carbon atom;    -   “Heteroaryl”: refers to an aryl group as defined above,        comprising at least one heteroatom, preferably chosen among O, N        or S;    -   “Heteroarylalkyl”: refers to an alkyl group substituted by an        heteroaryl group, which may be represented as heteroaryl-alkyl-;    -   “Heteroalkylaryl”: refers to an aryl group substituted by an        heteroalkyl group, which may be represented as        heteroalkyl-aryl-;    -   “Heteroalkenyl”: refers to an alkenyl group as defined above,        comprising at least one heteroatom, preferably chosen among O, N        or S;    -   “Heteroalkynyl”: refers to an alkynyl group as defined above,        comprising at least one heteroatom, preferably chosen among O, N        or S;    -   “Heteroalkyl”: refers to an alkyl group as defined above,        comprising at least one heteroatom, preferably chosen among O, N        or S;    -   “Hydroxyl” or “hydroxy”: refers to —OH;    -   “Imidazole”: refers to an aromatic heterocyclic compound of        formula C₃H₄N₂;    -   “Liquid”: refers to any medium having a viscosity measured at        room temperature in a range from 0.001 to 1000 Pa·s;    -   “Monomer”: refers to a molecule that form the basic repeating        unit for polymer. The term “monomer” refers to a compound having        at least one chemical function able to be engaged in a        polymerization reaction;    -   “Non-polar” or “apolar”: refers to any chemical compound having        a resulting dipolar moment ranging from 0 to 15;    -   “Oil” or “lubricant”: refers to any fatty substance, liquid at        room temperature and insoluble in water. In the present        invention, these terms refer to any fatty substance that may be        obtained from plants, minerals or animals;    -   “Oxo”: refers to a —(C═O)— group;    -   “Perfume”: refers to a substance able to emit and diffuse a        fragrant odor;    -   “Pyrrolidine”: refers to a heterocyclic compound of formula        C₄H₉N;    -   “Urea”: refers to a —NH—CO—NH— group;    -   “Spacer”: refers to a chemical group (in the present invention        referred to as Y) that separate two chemical function, herein        two urea functions;    -   “Stereogenic center”: refers to any atom comprising substituents        being in a spatial arrangement which is not superimposable on        its mirror image. In the present invention, the terms        “stereogenic center” also refer to a carbon atom having 4        different substituents;    -   “Thiol”: refers to a —SH moiety; and    -   “Thioxo”: refers to a —(C═S)— group.

DETAILED DESCRIPTION

Compounds

The present invention relates to a compound of general formula (I):

wherein:

Y represents aryl or heteroaryl, the aryl or heteroaryl group beingoptionally substituted by at least one group selected from alkyl,heteroalkyl, alkoxy, amino, alkylamino and halo; preferably Y representsa phenyl group optionally substituted by at least one group selectedfrom C₁-C₄ alkyl, C₁-C₄ heteroalkyl, C₁-C₄ alkoxy, C₁-C₄ dialkylaminoand halo; more preferably Y represents a phenyl group substituted by atleast one C₁-C₄ alkyl or halo group; and

R₁ and R₂ are each independently selected from H, alkyl, heteroalkyl,alkyloxycarbonylalkyl, alkyloxythiocarbonylalkyl.alkylthioxothiocarbonylalkyl and macromolecular groups, said groupsbeing optionally substituted by at least one group selected from alkyl,heteroalkyl, alkenyl, heteroalkenyl, aryl, heteroaryl, alkylaryl,alkynyl, heteroalkynyl arylalkyl, heteroarylalkyl, alkylheteroaryl,alkoxy, alkylthio, oxo and thioxo group; said substituents beingoptionally substituted by one or more group selected from guanidine,aryl, pyrrolidine, imidazole, hydroxyaryl, carboxy, selanyl, hydroxyl,amide, thiol, alkylthio, amino, deuterium or halo.

According to one embodiment, Y is aryl. According to one embodiment, Yis heteroaryl. According to one embodiment, Y is a phenyl group.According to one embodiment, Y is phenyl group linked to two ureafunctions at positions 1 and 3:

According to one embodiment, Y is a 2,4,6-substituted phenyl group.According to one embodiment, Y is a 4,6-substituted phenyl group.According to one embodiment, Y is a 2,6-substituted phenyl group.According to one embodiment, Y is a 2,4-substituted phenyl group.According to one embodiment, Y is a 2-substituted phenyl group.According to one embodiment, Y is a 4-substituted phenyl group.According to one embodiment, Y is a 6-substituted phenyl group.

According to one embodiment, Y is tolyl (i.e. a phenyl group substitutedby one methyl). According to one embodiment, Y is xylyl (i.e. a phenylgroup substituted by two methyl). According to one embodiment, Y ismesityl (i.e. a phenyl group substituted by three methyl). According toone embodiment, Y is a phenyl group substituted by one or more halo(i.e. fluoro (—F), chloro (—Cl), bromo (—Br) or iodo (—I) atom);preferably Y is a phenyl group substituted by two halo. According to oneembodiment, Y is a phenyl group substituted by one halo. According toone embodiment, Y is a phenyl group substituted by two halo. Accordingto one preferred embodiment, Y is a phenyl group substituted by twochloro atoms. According to one embodiment, Y is a 2,4,6-halo substitutedphenyl group.

According to one embodiment, R₁ and R₂ are macromolecular chains;preferably selected from polyacrylates, polymethacrylates, polyolefins,polycarbonates, polyether, polydienes, polysiloxanes, polyesters,polynorborenes, polycyclooctenes and polystyrenes. In the presentinvention, “macromolecular chains” or “polymer chains” refer to chainshaving a high molecular weight and resulting from the multiplerepetition of a repeating unit (monomer); said monomers being covalentlylinked each other. According to another embodiment, R₁ and R₂ are notmacromolecular chains. According to one embodiment, R₁ and R₂ are notpolymer chains. According to one embodiment, R₁ and R₂ are identical.According to one embodiment, R₁ and R₂ are different. According to oneembodiment, R₁ and R₂ are each independently selected from linear alkylor linear heteroalkyl chains, said chains being optionally substitutedby one or more oxo, thioxo and/or halo groups.

According to one embodiment, R₁ and R₂ are each independently selectedfrom H, alkyl, heteroalkyl, alkyloxycarbonylalkyl,alkyloxythiocarbonylalkyl and alkylthioxothiocarbonylalkyl, said groupsbeing optionally substituted by at least one group selected from alkyl,heteroalkyl, alkenyl, heteroalkenyl, aryl, heteroaryl, alkylaryl,alkynyl, heteroalkynyl arylalkyl, heteroarylalkyl, alkylheteroaryl,alkoxy, alkylthio, oxo and thioxo group; said substituents beingoptionally substituted by one or more group selected from guanidine,aryl, pyrrolidine, imidazole, hydroxyaryl, carboxy, selanyl, hydroxyl,amide, thiol, alkylthio, amino, deuterium or halo.

According to one embodiment, preferred compound of formula (I) arecompounds of formula (Ibis):

wherein:

Y is as defined above;

R₁′ and R₂′ are each independently selected from linear alkyl,heteroalkyl, alkenyl, heteroalkenyl, alkynyl and heteroalkynyl group,optionally substituted by one or more halo; preferably R₁′ and R₂′ areeach independently selected from linear alkyl or heteroalkyl group, saidlinear group being optionally substituted by one or more halo; morepreferably R₁′ and R₂′ are each independently selected from linearC₆-C₁₈ alkyl or heteroalkyl group, said linear group being optionallysubstituted by one or more terminal halo;

R₃′, R₃, R₄, R₄′ R₅′, R₅, R₆ and R₆′ are each independently selectedfrom H, alkyl, alkenyl, aryl, heteroalkyl, heteroalkenyl, heteroaryl,alkylaryl, arylalkyl, heteroarylalkyl or alkylheteroaryl, optionallysubstituted by guanidine, aryl, pyrrolidine, imidazole, hydroxyaryl,carboxy, selanyl, hydroxyl, amide, thiol, alkylthio, amino, deuterium orhalo; preferably R₃′, R₃, R₄, R₄′ R₅′, R₅, R₆ and R₆′ are eachindependently selected from H, C₁-C₁₂ alkyl substituted by at least onearyl, said aryl being optionally substituted by one or more halo ordeuterium;

Z₁, Z₁′, Z₂ and Z₂′ are each independently selected from O or S atoms;

n represents a positive integer from 0 to 10; preferably n is equal to0; and

optionally * stands for a stereogenic center.

According to one embodiment, when R₃ and R₃′ are different, * representsa stereogenic center. According to one embodiment, when R₄ and R₄′ aredifferent, * represents a stereogenic center. According to oneembodiment, when R₅ and R₅′ are different, * represents a stereogeniccenter. According to one embodiment, when R₆ and R₆′ are different, *represents a stereogenic center.

According to one embodiment, R₃′, R₃, R₄, R₄′ R₅′, R₅, R₆ and R₆′ areeach independently selected from H, guanidinealkyl, imidazolealkyl,aminoalkyl, carboxyalkyl, hydroxyalkyl, amidoalkyl, thioalkyl,selanylalkyl, pyrrolidinalkyl, phenylalkyl, benzylalkyl,hydroxyphenylalkyl, hydroxybenzylalkyl and indolylalkyl.

According to one embodiment, preferred compound of formula (Ibis) arecompounds of formula (Iter):

wherein:

Y, R₁′, R₂′ R₃′, R₃, R₄, R₄′ Z₁, Z₁′, Z₂, Z₂′ and * are as definedabove.

According to one embodiment, the compound of the invention isenantiopure (i.e. the compound of the invention is a single isomer withone chirality). According to one embodiment, the compound of theinvention is R,R-enantiomer. According to one embodiment, the compoundof the invention is S,S-enantiomer. According to one embodiment, thecompound of the invention is R,S-enantiomer. According to oneembodiment, the compound of the invention is S,R-enantiomer. Accordingto one embodiment, the compound of the invention is achiral. Accordingto one embodiment, the compound of the invention is racemic. Accordingto one embodiment, the compound of the invention is a mixture ofdiastereoisomers.

According to one embodiment, preferred compound of formula (I) arecompounds of formula (II):

wherein:

R_(a), R_(b), R_(c) and R_(d) are each independently selected from H,alkyl, heteroalkyl, alkoxy, amino, alkylamino and halo; preferably R_(b)and R_(d) are each independently selected from H, C₁-C₄ alkyl, C₁-C₄heteroalkyl, C₁-C₄ alkoxy, C₁-C₄ dialkylamino and halo; more preferablyR_(b) and R_(d) are each independently selected from at least one C₁-C₄alkyl or halo; and

R₁ and R₂ are as defined above.

According to one embodiment, R_(a) and R_(c) are both H. According toone embodiment, R_(a), R_(b), R_(c) and R_(d) are not all H. Accordingto one embodiment, R_(b) and R_(d) are not both H. According to oneembodiment, at least one of R_(b) and R_(d) is not H.

According to one embodiment, the compound of formula (II) isethylhexylureidoxylene (EHUX), also namedethylhexylureido-4,6-dimethylbenzene, of formula:

According to an alternative embodiment, the compound of formula (II) isnot EHUX. According to one embodiment, the compound of formula (II) isnot EHUT, also named ethylhexylureidotoluene, of formula:

According to one embodiment, the compound of formula (II) is not EHUTMB,also named ethylhexylureidotrimethylbenzene, of formula:

According to one embodiment, preferred compound of formula (II) arecompounds of formula (III):

wherein:

R_(b), R_(c), R₁ and R₂ are as defined above.

The present invention also refers to compounds of general formula (IV):

wherein:

R_(a), R_(b), R_(c) and R_(d) are as defined in formula (II);

R₁′ and R₂′ are each independently selected from linear alkyl,heteroalkyl, alkenyl, heteroalkenyl, alkynyl, heteroalkynyl andmacromolecular groups, optionally substituted by one or more halo;preferably R₁′ and R₂′ are each independently selected from linear alkylor linear heteroalkyl group, said linear group being optionallysubstituted by one or more halo; more preferably R₁′ and R₂′ are eachindependently selected from linear C₆-C₁₈ alkyl or heteroalkyl group,said linear group being optionally substituted by one or more terminalhalo;

R₃′, R₃, R₄, R₄′ R₅′, R₅, R₆ and R₆′ are each independently selectedfrom H, alkyl, alkenyl, aryl, heteroalkyl, heteroalkenyl, heteroaryl,alkylaryl, arylalkyl, heteroarylalkyl or alkylheteroaryl, optionallysubstituted by guanidine, aryl, pyrrolidine, imidazole, hydroxyaryl,carboxy, selanyl, hydroxyl, amide, thiol, alkylthio, amino, deuterium orhalo; preferably R₃′, R₃, R₄, R₄′ R₅′, R₅, R₆ and R₆′ are eachindependently selected from H, C₁-C₁₂ alkyl substituted by at least onearyl, said aryl being optionally substituted by one or more halo ordeuterium;

Z₁ and Z₁′ are each independently selected from O and S atoms;

Z₂ and Z₂′ are each independently selected from —NH—, O and S atoms;

n represents a positive integer from 0 to 10; preferably n is equal to0; and

optionally, * stands for a stereogenic center.

According one embodiment, R₁′ and R₂′ are each independently selectedfrom linear alkyl, heteroalkyl, alkenyl, heteroalkenyl, alkynyl andheteroalkynyl group, optionally substituted by one or more halo;preferably R₁′ and R₂′ are each independently selected from linear alkylor linear heteroalkyl group, said linear group being optionallysubstituted by one or more halo; more preferably R₁′ and R₂′ are eachindependently selected from linear C₆-C₁₈ alkyl or heteroalkyl group,said linear group being optionally substituted by one or more terminalhalo. According one embodiment, R₁′ and R₂′ are each independentlyselected from linear C₆-C₁₈ alkyl, C₆-C₁₈ heteroalkyl, C₆-C₁₈ alkenyl,C₆-C₁₈ heteroalkenyl, C₆-C₁₈ alkynyl, heteroalkynyl and macromoleculargroups, optionally substituted by one or more halo. According oneembodiment, R₁′ and/or R₂′ are not selected from C₁-C₅ alkyl, C₁-C₅heteroalkyl, C₁-C₅ alkenyl, C₁-C₅ heteroalkenyl, and C₁-C₅ alkynyl,heteroalkynyl. According one embodiment, R₁′ and/or R₂′ are not selectedfrom methyl, ethyl, propyl, butyl, or pentyl group.

According one embodiment, R_(b) and R_(d) are not both a hydrogen atom(—H). According one embodiment, at least one of R_(b) and R_(d) does notrepresent a hydrogen atom (—H).

According one embodiment, preferred compounds of general formula (IV)are compounds of formula (IV bis):

wherein R_(a), R_(b), R_(c), R_(d), R₁′, R₂′, R₃′, R₃, R₄ and R₄′ are asdefined in formula (IV).

According to one embodiment, preferred compounds of formula (IVbis) arecompounds of formula (IVter):

wherein R_(b), R_(d), R₁′, R₂′, R₃′, R₃, R₄ and R₄′ are as defined informula (IV).

According to one embodiment, R_(b) and R_(d) are each independentlyselected from H, alkyl, heteroalkyl, alkoxy, amino, alkylamino and halo;preferably R_(b) and R_(d) are each independently selected from H, C₁-C₄alkyl, C₁-C₄ heteroalkyl, C₁-C₄ alkoxy, C₁-C₄ dialkylamino and halo;more preferably R_(b) and R_(d) are each independently selected from atleast one C₁-C₄ alkyl or halo.

According to one embodiment, R_(1′) and R_(2′) are linear alkyl orlinear heteroalkyl chains. According to one embodiment, R_(1′) andR_(2′) are not ramified chains.

According to one embodiment, Z₁, Z₁′, Z₂ and Z₂′ represent O atoms.According to one embodiment, Z₁, Z₁′, Z₂ and Z₂′ represent S atoms.According to one embodiment, Z₁, Z₁′, Z₂ and Z₂′ represent S atoms.According to one embodiment, Z₁, and Z₁′ represent O atoms, and Z₂ andZ₂′ represent S atoms. According to one embodiment, Z₁, and Z₁′represent S atoms, and Z₂ and Z₂′ represent O atoms.

According to one embodiment, compounds of general formula (IV) aresymmetric. According to one embodiment, compounds of general formula(IV) are non-symmetric.

According to one embodiment, preferred compound of formula (IVter) arecompounds of formula (V-a):

wherein R_(b), R_(d), R₁′, R₂′, R₃′, R₃, R₄ and R₄′ are as definedabove.

In the present invention, compounds of formula (V-a) are called “esterbis-ureas”.

According to one embodiment, preferred compound of formula (IVter) arecompounds of formula (V-b):

wherein R_(b), R_(d), R₁′, R₂′, R₃′, R₃, R₄ and R₄′ are as definedabove.

In the present invention, compounds of formula (V-b) are called“dithioester bis-ureas”.

According to one embodiment, preferred compound of formula (IVter) arecompounds of formula (V-c):

wherein R_(b), R_(d), R₁′, R₂′, R₃′, R₃, R₄ and R₄′ are as definedabove.

In the present invention, compounds of formula (V-c) are called“thioester bis-ureas”.

According to one embodiment, preferred compound of formula (IVter) arecompounds of formula (V-d):

wherein R_(b), R_(d), R₁′, R₂′, R₃′, R₃, R₄ and R₄′ are as definedabove.

In the present invention, compounds of formula (V-d) are called“thionoester bis-ureas”.

According to one embodiment, preferred compounds of the invention arethose listed in Table 1 hereafter:

TABLE 1 Cpd reference Structure Name H3C5Tol

(2S,2′S)-dihexyl 2,2′-((((4- methyl-1,3- phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3- phenylpropanoate) H3C6Tol

(2S,2′S)-diheptyl 2,2′-((((4- methyl-1,3- phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3- phenylpropanoate) H3C7Tol

(2S,2′S)-dioctyl 2,2′-((((4- methyl-1,3- phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3- phenylpropanoate) H3C7Xyl

(2S,2′S)-dioctyl 2,2′-((((4,6- dimethyl-1,3-phenylene)bis(azanediyl))bis (carbonyl))bis(azanediyl))bis(3-phenylpropanoate) H3C7Cl

(2S,2′S)-dioctyl 2,2′-((((4,6- dichloro-1,3-phenylene)bis(azanediyl))bis (carbonyl))bis(azanediyl))bis(3-phenylpropanoate) H3C8Tol

(2S,2′S)-dinonyl 2,2′-((((4- methyl-1,3- phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3- phenylpropanoate) H3C8Xyl

(2S,2′S)-dinonyl 2,2′-((((4,6- dimethyl-1,3-phenylene)bis(azanediyl))bis (carbonyl))bis(azanediyl))bis(3-phenylpropanoate) H3C9Tol

(2S,2′S)-didecyl 2,2′-((((4- methyl-1,3- phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3- phenylpropanoate) H3C10Tol

(2S,2′S)-diundecyl 2,2′-((((4- methyl-1,3- phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3- phenylpropanoate) H3C11Tol

(2S,2′S)-didodecyl 2,2′-((((4- methyl-1,3- phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3- phenylpropanoate) H3C11Xyl

(2S,2′S)-didodecyl 2,2′-((((4,6- dimethyl-1,3-phenylene)bis(azanediyl))bis (carbonyl))bis(azanediyl))bis(3-phenylpropanoate) H3C12Tol

(2S,2′S)-ditridecyl 2,2′-((((4- methyl-1,3- phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3- phenylpropanoate) H3C13Tol

(2S,2′S)-ditetradecyl 2,2′-((((4- methyl-1,3-phenylene)bis(azanediyl))bis (carbonyl))bis(azanediyl))bis(3-phenylpropanoate) H3C15Tol

(2S,2′S)-dihexadecyl 2,2′-((((4- methyl-1,3-phenylene)bis(azanediyl))bis (carbonyl))bis(azanediyl))bis(3-phenylpropanoate) H3C15Xyl

(2S,2′S)-dihexadecyl 2,2′- ((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis (carbonyl))bis(azanediyl))bis(3-phenylpropanoate) H3C17Tol

(2S,2′S)-dioctadecyl 2,2′-((((4- methyl-1,3-phenylene)bis(azanediyl))bis (carbonyl))bis(azanediyl))bis(3-phenylpropanoate) H3C7d₅- PheTol

(2S,2′S)-dioctyl 2,2′-((((4- methyl-1,3- phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3- pentadeuteriumphenylpropanoate)Br3C11Tol

(2S,2′S)-bis(12,12,12- tribromododecyl) 2,2′-((((4- methyl-1,3-phenylene)bis(azanediyl))bis (carbonyl))bis(azanediyl))bis(3-phenylpropanoate) Br3C11Xyl

(2S,2′S)-bis(12,12,12- tribromododecyl) 2,2′-((((4,6- dimethyl-1,3-phenylene)bis(azanediyl))bis (carbonyl))bis(azanediyl))bis(3-phenylpropanoate) Br3C11Cl

(2S,2′S)-bis(12,12,12- tribromododecyl) 2,2′-((((4,6- dichloro-1,3-phenylene)bis(azanediyl))bis (carbonyl))bis(azanediyl))bis(3-phenylpropanoate) Cl3C11Xyl

(2S,2′S)-bis(12,12,12- trichlorododecyl) 2,2′-((((4,6- dimethyl-1,3-phenylene)bis(azanediyl))bis (carbonyl))bis(azanediyl))bis(3-phenylpropanoate)

In Table 1, the term “Cpd” means compound.

The compounds of Table 1 were named using ChemBioDraw® Ultra version12.0 (PerkinElmer).

Composition

The present invention also refers to a composition comprising at leastone compound of the invention as defined above, and a non-polar liquid.Especially, the present invention refers to a composition comprising anon-polar liquid and at least one compound of formula (IV) or (IV bis)as defined above.

According to one embodiment, the composition comprises one singlecompound of the invention as defined above, and a non-polar liquid.According to one embodiment, the composition comprises two compounds ofthe invention as defined above, and a non-polar liquid.

According to one embodiment, the composition is constituted by anon-polar liquid and at least one compound of the invention as describedabove.

According to one embodiment, the composition is constituted by anon-polar liquid and at least one compound of formula (IV) or of formula(IV bis) as defined above.

According to one embodiment, the non-polar liquid is liquid orsemi-liquid. According to one embodiment, the non-polar liquid isselected methylcyclohexane and dodecane. According to one embodiment,the non-polar liquid is selected from an oil (or lubricant), a grease, amonomer, a thermosetting resin, a perfume or a fuel.

According to one embodiment, the oil is selected from mineral(hydrocarbon), natural (fatty ester) or synthetic (poly(alpha olefin))oils. According to one embodiment, the monomer selected from acrylates,methacrylates and styrenics.

In the present invention, the relative viscosity is measured by usingAnton paar AMVn falling-ball microviscometer with a 0.16 mm diametercapillary. Three measurements are carried out at an angle of +20° and−20°. The viscosity value is reported as an average of thosemeasurements.

According to one embodiment, the non-polar liquid when not comprising acompound of the invention, has a viscosity at room temperature rangingfrom 0.001 to 1000 Pa·s; preferably from 0.01 to 100 Pa·s. According toone embodiment, the non-polar liquid when not comprising a compound ofthe invention, has a viscosity at room temperature ranging from 1 to 100Pa·s, preferably from 10 to 100 Pa·s, from 20 to 100 Pa·s, from 30 to100 Pa·s, from 40 to 100 Pa·s, from 50 to 100 Pa·s, from 60 to 100 Pa·s,from 70 to 100 Pa·s, from 80 to 100 Pa·s, or from 90 to 100 Pa·s.According to one embodiment, the non-polar liquid when not comprising acompound of the invention, has a viscosity at room temperature rangingfrom 0.01 to 90 Pa·s, preferably from 0.01 to 80 Pa·s, from 0.01 to 70Pa·s, from 0.01 to 60 Pa·s, from 0.01 to 50 Pa·s, from 0.01 to 40 Pa·s,from 0.01 to 30 Pa·s, from 0.01 to 20 Pa·s, from 0.01 to 10 Pa·s, orfrom 0.01 to 1 Pa·s.

According to one embodiment, the composition of the invention (i.e. thenon-polar liquid comprising at least one compound of the invention) hasa relative viscosity at room temperature ranging from 1 to 100;preferably from 1 to 10.

According to one embodiment, in the composition of the invention, thecompound of the invention is at a concentration in the non-polar liquid,ranging from more than 0 to 5%; preferably from 0.01 to 1% by weight tothe total weight of the composition. According to one embodiment, theconcentration of the compound of the invention in the non-polar liquidis about 0.01% by weight to the total weight of the composition.According to one embodiment, in the composition of the invention, thecompound of the invention is at a concentration in the non-polar liquid,ranging from 0.001 to 5%; preferably from 0.01 to 5%, from 0.1 to 5%,from 1 to 5%, from 2 to 5%, from 3 to 5%, from 4 to 5%, by weight to thetotal weight of the composition. According to one embodiment, in thecomposition of the invention, the compound of the invention is at aconcentration in the non-polar liquid of 1, 2, 3, 4, or 5%, by weight tothe total weight of the composition. According to one embodiment, theconcentration of the compound of the invention in the non-polar liquidis about 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%or 1% by weight to the total weight of the composition.

According to one embodiment, the compound of the invention is at a molarconcentration in the non-polar liquid, preferably in methylcyclohexaneor dodecane, ranging from more than 0 to 50 mM; preferably from 0.1 to10 mM. According to one embodiment, the concentration of the compound ofthe invention in the non-polar liquid is about 0.1 mM. According to oneembodiment, the compound of the invention is at a molar concentration inthe non-polar liquid, preferably in methylcyclohexane or dodecane,ranging from 0.01 to 50 mM, preferably from 0.01 to 50 mM, from 0.1 to50 mM, from 1 to 50 mM, from 10 to 50 mM, from 20 to 50 mM, from 30 to50 mM, or from 40 to 50 mM. According to one embodiment, theconcentration of the compound of the invention in the non-polar liquidis from 0.1 to 10 mM, preferably from 1 to 10 mM, preferably from 2 to10 mM, 3 to 10 mM, 4 to 10 mM, 5 to 10 mM, 6 to 10 mM, 7 to 10 mM, 8 to10mM or 9 to 10 mM. According to one embodiment, the concentration ofthe compound of the invention in the non-polar liquid is 1, 2, 3, 4, 5,6, 7, 8, 9 or 10 mM.

According to one embodiment, the composition may further comprisesuitable additives.

Process for Manufacturing Compounds of the Invention

The present invention also relates to a process for manufacturingcompounds of formula (IVbis) as defined above wherein Z₁, Z₁′, Z₂ andZ₂′ represent O atom, comprising reacting at least one ester ammoniumsalt of formula (A-1):

-   -   wherein R₁′, R₃′ and R₃, are as defined above; and X⁻ is an        anion, preferably selected from chloride, bromide, sulfate,        hydrogenosulfate and sulfonate; more preferably X⁻ is tosylate;

with

-   -   (a) either diisocyanate of general formula (A-2):

-   -   -   wherein Y is as defined above;

    -   (b) or a mixture of reagents allowing the in situ preparation of        diisocyanate of general formula (A-2).

According to one embodiment, the ester ammonium salt is an esterammonium tosylate salt:

wherein R₁′, R₃′ and R₃, are as defined above;

According to one embodiment, the step (b) comprises the mixture of acompound having a carbonyl function and a diamine of formula (A-3):

wherein Y is as defined above.

According to one embodiment, the ester ammonium salt is an esterammonium tosylate salt:

-   -   wherein R₁′, R₃′ and R₃, are as defined above.

According to one embodiment, the compound having a carbonyl function isselected from oxychlorides and carbonates.

According to one embodiment, the compound having a carbonyl function isphosgene:

According to one embodiment, the compound having a carbonyl function isbis(trichloromethyl)carbonate:

According to one embodiment, compound A-2 is compound A-2bis:

wherein R_(a), R_(b), R_(c) and R_(d) are as defined above.

According to one embodiment, compound A-2 is an aryl substituted by atleast two isocyanato groups, preferably an alkyl benzene comprising twoisocyanato groups; more preferably compound A-2 is2,4-diisocyanato-1-methylbenzene.

According to one embodiment, compound A-3 is an aryl substituted by atleast two amino groups, preferably an alkyl benzene comprising two aminogroups. According to one embodiment, compound A-3 is of formula(A-3bis):

wherein R_(a), R_(b) R_(c) and R_(d), are as defined above.

According to one embodiment, the ester ammonium salt of formula (A-1) issynthetized in a preliminary step comprising reacting an amino acid andan alcohol.

According to one embodiment, the amino acid is selected from alanine(Ala), arginine (Arg), asparagine (Asn), aspartate (Asp), cysteine(Cys), glutamate (Glu), glutamine (Gln), glycine (Gly), histidine (His),isoleucine (Ile), leucine (Leu), lysine (Lys), methionine (Met),phenylalanine (Phe), proline (Pro), pyrrolysine, selenocysteine (Sec),serine (Ser), threonine (Thr), tryptophan (Trp), tyrosine (Tyr) andvaline (Val); preferably glycine, valine, phenylalanine, tyrosine,histidine, tryptophan, iso-leucine and methionine. According to oneembodiment, the amino acid is phenylalanine.

According to one embodiment, the alcohol is hydroxyalkane, preferablylinear alkyl chains having a hydroxyl group. According to oneembodiment, the preliminary step comprises reacting 1 equivalent ofamino acid and 1.1 equivalent of alcohol.

According to one embodiment, the preliminary step further comprises asolvent, preferably a non-polar solvent; more preferably the solvent istoluene.

According to one embodiment, the preliminary step is carried out at atemperature higher than room temperature, preferably at a temperatureranging from 30° C. to 150° C. According to one embodiment, thepreliminary step is carried out at a temperature higher than roomtemperature, preferably at a temperature ranging from 40° C. to 150° C.,preferably from 50° C. to 150° C., from 60° C. to 150° C., from 70° C.to 150° C., from 80° C. to 150° C., from 90° C. to 150° C., from 100° C.to 150° C., from 110° C. to 150° C., from 120° C. to 150° C., from 130°C. to 150° C., or from 140° C. to 150° C. According to one embodiment,the preliminary step is carried out under reflux.

According to one embodiment, the preliminary step is carried out duringa period time ranging from 1 h to 48 h, preferably from 1 h to 24 h,more preferably for 12 h. According to one embodiment, the preliminarystep is carried out during a period time ranging from 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47 or 48 h.

Step (a)

According to one embodiment, the step (a) is carried out in a solvent,preferably an organic solvent, more preferably in tetrahydrofuran (THF).

According to one embodiment, the step (a) further comprises the use ofan amine, preferably triethylamine.

Step (b)

According to one embodiment, the step (b) is carried out in a solvent,preferably an organic solvent, more preferably in dichloromethane (DCM).

According to one embodiment, the step (b) further comprises the use ofan amine, preferably NN-Diisopropylethylamine (DIEA).

Uses

As mentioned above, the present invention relates to the use as athermo-thickening agent of a compound or a composition of the inventionas defined above.

Especially, the present invention refers to the use as athermo-thickening agent of a compound of general formula (I):

wherein Y, R₁ and R₂ are as defined above.

According to one embodiment, the compound is of general formula (II):

wherein R₁, R₂ R_(a), R_(b), R_(c) and R_(d) are as defined above.

Especially, the present invention refers to the use as athermo-thickening agent of a compound of general formula (IV) and/orformula (IVbis) as defined above.

According to one embodiment, the compound or the composition of theinvention is useful for thermo-thickening a non-polar liquid; preferablyan oil (or lubricant), a grease, a monomer, a thermosetting resin, aperfume or a fuel.

According to one embodiment, the compound or the composition of theinvention is useful (a) for thickening a non-polar liquid at atemperature ranging from 0° C. to 50° C., preferably from 20° C. to 45°C., and/or for maintaining the viscosity obtained at step (a) when thetemperature increases. According to one embodiment, the compound or thecomposition of the invention is useful (a) for thickening a non-polarliquid at a temperature ranging from 0° C. to 50° C., preferably from20° C. to 45° C., and/or for maintaining the viscosity obtained at step(a) when the temperature is higher from 50° C., preferably ranges from50° C. to 100° C. According to one embodiment, the compound or thecomposition of the invention is useful (a) for thickening a non-polarliquid at a temperature ranging from 0° C. to 50° C., preferably from20° C. to 45° C., and/or for avoiding that, upon temperature rise attemperature higher than 50° C., the viscosity obtained at step (a)decreases to the same extend than it decreases in absence of anythermo-thickening agent.

According to one embodiment, the compound or the composition of theinvention is useful for thermo-thickening at a temperature ranging from5° C. to 100° C.; preferably from 10° C. to 60° C.; more preferably from20° C. to 50° C. According to one embodiment, the compound or thecomposition of the invention is useful for thermo-thickening at atemperature ranging from 10° C. to 100° C., preferably from 20° C. to100° C., 30° C. to 100° C., 40° C. to 100° C., 50° C. to 100° C., 60° C.to 100° C., 70° C. to 100° C., 80° C. to 100° C., or 90° C. to 100° C.According to one embodiment, the compound or the composition of theinvention is useful for thermo-thickening at a temperature of 20, 25,30, 35, 40, 45 or 50° C.

According to one embodiment, the compound or the composition of theinvention is further useful for improving the cold flow property of anon-polar liquid. According to one embodiment, the compound or thecomposition of the invention is useful for improving the cold flowproperty of a non-polar liquid. According to one embodiment, thecompound or the composition of the invention is useful for maintainingand/or increasing the viscosity of a non-polar liquid during itsheating.

Advantageously, the compounds or composition of the invention allowacting as thermo-thickening agent while ensuring efficient mechanicalengine operation both at low and high temperatures.

Advantageously, the compounds or composition of the invention allow toslow down the evaporation of a non-polar liquid, especially a perfume.

Kit

The present invention also relates to a kit comprising in onecompartment a compound of the invention as defined above, and in asecond compartment a non-polar liquid as defined above.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a theoretical graph of the variation of the viscosity infunction of the temperature for a liquid (dotted line) and for the sameliquid comprising a thermo-thickening compound of the invention (solidline).

FIG. 2 is a graph showing the evolution of flow time in function of thetemperature for dodecane and methylcyclohexane and correspondingsolutions comprising H3C11Xyl.

FIG. 3 is a graph showing the relative viscosity in function of thetemperature for dodecane or methylcyclohexane solutions comprisingH3C7Xyl, H3C11Xyl or H3C15Xyl.

FIG. 4 is a graph showing the evolution of G′ and G″ modulus for asolution of H3C11Xyl in dodecane (4.1 g/L) in function of frequency(rad/s).

FIG. 5 is a graph showing the evolution of complex viscosity for asolution of H3C11Xyl in dodecane (4.1 g/L) in function of frequency(rad/s).

EXAMPLES

The present invention is further illustrated by the following examples.

Part 1: Chemistry

Abbreviations

Ala Alanine;

AcOEt Ethyl acetate;

Ar Aromatic group;

CDCl₃ Chloroform;

DCM Dichloromethane;

DIEA N,N-Diisopropylethylamine;

DIPA Diisopropylamine;

DMSO Dimethylsulfoxyde;

ESI Electrospray Ionization;

eq. Equivalent;

HMPA Hexamethylphosphoramide;

HRMS High-resolution mass spectrometry;

LDA Lithium diisopropylamide;

Leu et i-Leu Leucine and iso-Leucine;

M Molar;

min Minute(s);

MS Mass spectrometry;

NMR Nuclear magnetic resonance;

PE Petroleum ether;

Phe Phenylalanine;

PhGly Phenylglycine;

PTSA p-Toluenesulfonic acid;

TDI Toluene diisocyanate;

THF Tetrahydrofurane;

THP Tetrahydropyrane.

Materials and Methods

All amino acids were purchased from Sigma-Aldrich or Alfa Aesar (99%purity) and used as received. TDI was purchased from Sigma Aldrich(purity≥98%) and was used directly. Chromatography-grade solvents wereused as received. Dried CH₂Cl₂ and THF were obtained from an SPS solventpurification system (IT-Inc) and stored on 4 Å molecular sieves. NEt₃and DIEA were dried by distillation over CaH2 and stored over 4 Åmolecular sieves.

NMR Spectroscopy

NMR spectra were recorded on a Bruker Avance 400, 300 or 200spectrometers and calibrated to the residual solvent peak. Peaks arereported in ppm with their corresponding multiplicity (s: singlet; d:doublet, t: triplet; q: quartet; quint: quintet; hept: heptuplet; dt:doublet of triplets; td: triplet of doublets), integration, andrespective J coupling constants are given in hertz.

HRMS Spectrometer

Exact mass measurements (HRMS) were obtained on TQ R30-10 HRMSspectrometer by ESI+ ionization and are reported in m/z for the majorsignal.

Flash Chromatography

The flash chromatography purification was made with a Grace Revelerisand columns of the same brand. The water was purified using a milli-Qsystem.

Fourier Transform InfraRed Spectroscopy (FT-IR)

FT-IR measurements were performed on a Nicolet iS10 spectrometer in aCaF2 cell of 1.0 mm pathlength and are corrected for air, solvent andcell absorption.

Rheology Measurements

Rheology measurements were performed on a Haake RS600 rheometer equippedwith a sandblasted stainless steel cone/plate geometry with a 35 mmdiameter, a 53 μm gap and a 2° angle. The temperature is controlled witha Peltier thermostat.

Viscosimetry Measurements

Viscosimetry measurements were recorded using an Anton paar AMVnfalling-ball microviscometer with a 0.16 mm diameter capillary, withthree measurements at an angle of +20° and −20°. Results are reported asan average of those six measurements.

Example 1 General Procedures for Preparing Ester Bis-Ureas

1.1. Synthesis of Ester Ammonium Tosylate Salts (Preliminary Step)

This synthesis was adapted from: S. Cantekin, H. M. M. ten Eikelder, A.J. Markvoort, M. A. J. Veld, P. A. Korevaar, M. M. Green; A. R. A.Palmans, E. W. Meijer, Angew. Chem. Int. Ed. 2012, 51, 6426-6431.

1 eq. of amino acid, 1.1 eq. of alcohol and 1.1 eq. of PTSA.H₂O wereadded to toluene (0.15M) and the mixture was stirred under refluxequipped with a Dean-Stark apparatus for 12 h. The mixture was thenconcentrated under reduced pressure and diluted in Et₂O. The solutionwas put into ice to precipitate for a couple of hours. The precipitatewas then filtered, washed with cold Et₂O and dried under vacuum.

1.2. Synthesis of Ester Bis-Ureas with a Toluene Spacer (Method A)

This synthesis was adapted from: F. Lortie, S. Boileau, L. Bouteiller,C. Chassenieux, B. Demé, G. Ducouret, M. Jalabert, F. Laupretre, P.Terech, Langmuir 2002, 18, 7218-7222.

2.2 eq. of the ammonium ester tosylate (obtained according to method asdefined above) was dissolved in anhydrous THF (0.05 M) under argon. 2.2eq. of NEt₃ and 1 eq. of TDI were added to the mixture. The mixture wasstirred at room temperature for 48 h. The mixture was then concentratedunder reduced pressure and either purified by column chromatography orrecrystallized from acetonitrile.

1.3. Synthesis of Ester Bis-Ureas with Other Spacers (Method B)

This synthesis was adapted from: I. Giannicchi, B. Jouvelet, B. Isare,M. Linares, A. Dalla Cort, L. Bouteiller, Chem. Commun. 2014, 50,611-613.

Under argon atmosphere, a 70 mM solution of the diaminobenzenederivative and 2 eq. of DIEA in DCM was added at 2.5 mL/h to a 60 mMsolution of 0.66 eq. of triphosgene in DCM. The mixture was stirred for1 h after addition and a 0.3 M solution of 2.1 eq. of the ammonium estertosylate and 6.3 eq. of DIEA in DCM was added to the mixture. Thesolution was concentrated under reduced pressure and the product waseither purified by column chromatography or recrystallized fromacetonitrile.

Example 2 Synthesis of Ester Ammonium Tosylate Salts

2.2. Linear Compounds

2.2.1. Synthesized from Phenylalanine

Hexyl (S)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as describedabove, using commercially available hexanol and (S)-Phenylalanine. Theproduct was obtained as a white powder.

Heptyl (S)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as describedabove, using commercially available heptanol and (S)-Phenylalanine. 3.41g (99%) of product were obtained as a white powder.

¹-H NMR (400 MHz, CDCl₃) δ 8.24 (s, 3H, NH3), 7.74 (d, 2H, Ar—H, J=7.8Hz), 7.20-7.03 (m, 7H, Ar—H), 4.31-4.18 (m, 1H, NH3-CH), 3.94-3.77 (m,2H, COO—CH2), 3.24 (dd, 1H, NH3-CH—CH2, J=14.0, 5.3 Hz), 3.04 (dd,NH3-CH—CH2, 1H, J=14.0, 8.2 Hz), 2.32 (s, 3H, Ar—CH3), 1.37-1.07 (m,12H, CH2), 1.07-0.97 (m, 2H, CH2), 0.88 (t, 3H, CH3, J=6.5 Hz). ¹³C NMR(101 MHz, CDCl₃) δ 169.02, 141.70, 140.33, 134.48, 129.57, 128.92,128.69, 127.34, 126.34, 54.34, 36.53, 32.07, 29.86, 29.80, 29.65, 29.50,29.37, 28.23, 25.75, 22.83, 21.45, 14.25.

Octyl (S)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as describedabove, using commercially available octanol and (S)-Phenylalanine. 5.94g (95%) of product were obtained as a white powder.

¹H NMR (300 MHz, CDCl₃) δ 8.44 (s, 3H, NH3), 7.50 (d, 2H, Ar—H, 2J=7.6Hz), 7.38-7.02 (m, 7H, Ar—H), 4.25 (t, 1H, NH3-CH, ²J=6.6 Hz), 3.99 (t,2H, COO—CH2, ²J=6.3 Hz), 3.08 (AB spin sytem, 2H, NH3-CH—CH2, ²J=8.1Hz), 1.80 (quin, 2H, COO—CH2-CH2, ²J=1.8 Hz), 2.27 (s, 3H, Ar—CH3), 1.39(quin, 2H, COO—CH2-CH2-CH2, ²J=6.5 Hz), 1.30-1.00 (m, 10H, CH2), 0.85(t, 3H, CH3, ²J=7.0 Hz). ¹³C NMR (101 MHz, CDCl₃) δ 169.01, 141.69,140.33, 134.49, 129.56, 128.91, 128.67, 127.33, 126.33, 66.37, 54.33,31.93, 29.28, 29.25, 28.21, 25.72, 22.77, 21.44, 14.22.

Nonyl (S)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as definedabove, using commercially available nonanol and (S)-Phenylalanine. 5.32g (91%) of product were obtained as a white powder.

¹H NMR (300 MHz, CDCl₃) δ 8.24 (s, 3H, NH3), 7.75 (d, 2H, Ar—H, ²J=8.1Hz), 7.19-7.03 (m, 7H, Ar—H), 4.30-4.20 (m, 1H, NH3-CH), 3.95-3.80 (m,2H, COO—CH2), 3.15 (AB spin sytem, 2H, NH3-CH—CH2), 2.33 (s, 3H,Ar—CH3), 1.39-1.00 (m, 14H, CH2), 0.90 (t, 3H, CH3, ²J=7.0 Hz)¹³C NMR(101 MHz, CDCl₃) δ 168.86, 141.53, 140.23, 134.32, 129.44, 128.79,128.56, 127.22, 126.21, 66.26, 54.20, 36.39, 31.87, 29.44, 29.28, 29.21,28.10, 25.60, 22.67, 21.31, 14.11.

Decyl (S)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as definedabove, using commercially available decanol and (S)-Phenylalanine. 3.22g (59%) of product were obtained as a white powder.

¹H NMR (300 MHz, CDCl₃) δ 8.24 (s, 3H, NH3), 7.75 (d, 2H, Ar—H, ²J=8.1Hz), 7.19-7.03 (m, 7H, Ar—H), 4.30-4.20 (m, 1H, NH3-CH), 3.95-3.80 (m,2H, COO—CH2), 3.15 (AB spin sytem, 2H, NH3-CH—CH2), 2.33 (s, 3H,Ar—CH3), 1.39-1.00 (m, 16H, CH2), 0.90 (t, 3H, CH3, ²J=7.0 Hz; ¹³C NMR(101 MHz, CDCl₃) δ 169.01, 141.67, 140.36, 134.47, 129.57, 128.92,128.69, 127.35, 126.34, 66.39, 54.34, 36.53, 32.04, 29.71, 29.62, 29.46,29.35, 28.23, 25.74, 22.82, 21.45, 14.25.

Undecyl (S)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as definedabove, using commercially available undecanol and (S)-Phenylalanine.2.13 g (82%) of product were obtained as a white powder.

¹H NMR (300 MHz, CDCl₃) δ 8.24 (s, 3H, NH3), 7.75 (d, 2H, Ar—H, ²J=8.1Hz), 7.19-7.03 (m, 7H, Ar—H), 4.30-4.20 (m, 1H, NH3-CH), 3.95-3.80 (m,2H, COO—CH2), 3.15 (AB spin sytem, 2H, NH3-CH—CH2), 2.33 (s, 3H,Ar—CH3), 1.39-1.00 (m, 18H, CH2), 0.90 (t, 3H, CH3, ²J=7.0 Hz). ¹³C NMR(101 MHz, CDCl₃) δ 169.01, 141.70, 140.33, 134.49, 129.57, 128.92,128.67, 127.33, 126.34, 66.38, 54.34, 36.53, 32.06, 29.82, 29.79, 29.77,29.63, 29.50, 29.36, 25.74, 22.83, 21.44, 14.25.

Dodecyl (S)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as definedabove, using commercially available dodecanol and (S)-Phelylalanine10.62 g (86%) of product were obtained as a white powder.

¹H NMR (400 MHz, CDCl₃) δ 8.24 (s, 3H, NH3), 7.74 (d, 2H, Ar—H, J=8.2Hz), 7.20-7.04 (m, 6H, Ar—H), 4.29-4.19 (m, 1H, NH3-CH), 3.93-3.77 (m,2H, COO—CH2), 3.24 (dd, 1H, NH3-CH—CH2, J=14.0, 5.3 Hz), 3.04 (dd, 1H,NH3-CH—CH2, J=14.0, 8.4 Hz), 2.32 (s, 3H, Ar—CH3), 1.38-1.08 (m, 14H,CH2), 1.08-0.96 (m, 2H, CH2), 0.89 (t, 3H CH3, J=6.8 Hz). ¹³C NMR (101MHz, CDCl₃) δ 169.02, 141.70, 140.31, 134.52, 129.56, 128.90, 128.65,127.30, 126.33, 66.35, 54.34, 36.53, 32.05, 29.81, 29.78, 29.76, 29.62,29.49, 29.35, 28.21, 25.73, 22.81, 21.43, 14.24.

Dodecyl (R)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as definedabove, using commercially available dodecanol and (R)-Phenylalanine.2.12 g (86%) of product were obtained as a white powder.

¹H NMR (300 MHz, CDCl₃) δ 8.21 (s, 3H, NH3), 7.72 (d, 2H, Ar—H, ²J=8.1Hz), 7.18-7.03 (m, 7H, Ar—H), 4.30-4.16 (m, 1H, NH3-CH), 3.94-3.76 (m,2H, COO—CH2), 3.14 (AB spin sytem, 2H, NH3-CH—CH2), 2.31 (s, 3H,Ar—CH3), 1.40-0.97 (m, 28H, CH2), 0.87 (t, 2H, CH3, ²J=7.0 Hz). ¹³C NMR(101 MHz, CDCl₃) δ 169.02, 141.70, 140.32, 134.52, 129.56, 128.91,128.66, 127.31, 126.34, 66.36, 54.34, 36.53, 32.05, 29.76, 29.63, 29.49,29.35, 28.22, 25.73, 22.82, 21.43, 14.24.

Tridecyl (S)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as definedabove, using commercially available decanol and (S)-Phenylalanine. 4.14g (88%) of product were obtained as a white powder.

¹H NMR (400 MHz, CDCl₃) δ 8.18 (s, 3H, NH3), 7.76 (d, 2H, Ar—H, J=7.9Hz), 7.23-7.05 (m, Ar—H, 7H), 4.27 (dd, NH3-CH, 1H, J=8.1, 5.3 Hz), 3.88(m, 2H, COO—CH2), 3.27 (dd, 1H, NH3-CH—CH2, J=14.1, 5.3 Hz), 3.07 (dd,1H, NH3-CH—CH2, J=14.1, 8.2 Hz), 2.35 (s, 3H, Ar—CH3), 1.43-1.11 (m,20H, CH2), 1.06 (q, 2H, CH2, J=7.7 Hz), 0.91 (t, 3H, CH3, J=6.6 Hz). ¹³CNMR (101 MHz, CDCl₃) δ 141.69, 140.35, 134.45, 129.57, 128.93, 128.70,127.36, 126.32, 66.40, 54.34, 29.84, 29.82, 29.80, 29.77, 29.63, 29.50,29.36, 28.23, 25.75, 22.83, 21.45, 14.25.

Tetradecyl (S)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as definedabove, using commercially available decanol and (S)-Phenylalanine. 1.47g (33%) of product were obtained as a white powder.

¹H NMR (400 MHz, CDCl₃) δ 8.24 (s, 3H, NH3), 7.74 (d, 2H, Ar—H, J=8.0Hz), 7.21-7.02 (m, 7H, Ar—H), 4.24 (dd, 1H, NH3-CH, J=8.2, 5.3 Hz),3.95-3.76 (m, 2H, COO—CH2), 3.24 (dd, 1H, NH3-CH—CH2, J=14.1, 5.3 Hz),3.05 (dd, 1H, NH3-CH—CH2, J=14.0, 8.2 Hz), 2.33 (s, 3H, Ar—CH3),1.45-1.09 (m, 21H, CH2), 1.04 (q, 2H, CH2, J=7.7 Hz), 0.89 (t, 3H, CH3,J=6.7 Hz). ¹³C NMR (101 MHz, CDCl₃) δ 141.70, 140.35, 134.45, 129.58,128.93, 128.70, 127.36, 126.33, 66.40, 54.33, 29.85, 29.83, 29.81,29.78, 29.64, 29.51, 29.37, 28.24, 25.75, 22.83, 21.45, 14.25.

Hexadecyl (S)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as definedabove, using commercially available decanol and (S)-Phenylalanine. 5.84g (92%) of product were obtained as a white powder.

¹H NMR (300 MHz, CDCl₃) δ 8.21 (s, 3H, NH3), 7.72 (d, 2H, Ar—H, ²J=8.2Hz), 7.16-7.034 (m, 7H, Ar—H), 4.27-4.17 (m, 1H, NH3-CH), 3.91-3.77 (m,2H, COO—CH2), 3.12 (AB spin sytem, 2H, NH3-CH—CH2), 2.31 (s, 3H,Ar—CH3), 1.35-1.06 (m, 28H, CH2), 0.86 (t, 3H, CH3, ²J=7.0 Hz). ¹³C NMR(101 MHz, CDCl₃) δ 168.88, 141.56, 140.21, 134.34, 129.44, 128.79,128.56, 127.22, 126.21, 66.26, 54.21, 36.40, 31.94, 29.73, 29.71, 29.68,29.66, 29.52, 29.37, 29.24, 28.11, 25.62, 22.70, 21.32, 14.12.

Octadecyl (S)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as definedabove, using commercially available 1-octadecanol and (S)-Phenylalanine.The product is obtained as a white powder.

2.2.2. Synthesized from Other Aminoacids

Octyl (S)-d₅-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as definedabove, using commercially available octanol and (S)-d₅-Phenylalanine.2.32 g (85%) of product were obtained as a white powder.

¹H NMR (300 MHz, DMSO-d₆) δ 8.45 (s, 3H, NH3), 7.23 (d, 2H, Ar—H, ²J=8.1Hz), 6.84 (d, 2H, Ar—H, ²J=8.0 Hz), 4.28 (t, 1H, NH3-CH, ²J=6.9 Hz),4.02 (t, 2H, COO—CH2, ²J=6.4 Hz), 3.10 (AB system, 2H, NH3-CHCH2), 2.29(s, 3H, Ar—CH3), 1.48-1.34 (m., 2H, COO—CH2CH2), 1.34-1.06 (m, 10H,CH2), 0.87 (t, 12H, CH3, ²J=6.8 Hz) ¹³C NMR (75 MHz, DMSO-d₆) δ 127.81,125.22, 65.27, 52.98, 35.78, 30.91, 28.23, 27.49, 24.82, 21.79, 20.48,13.64.

2.2.3. Halogen-Functionalized Compounds

12-Tribromododecyl (S)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as definedabove, using 12-tribromododecanol and (S)-phenylalanine. 6.57 g (85%) ofproduct were obtained as a white powder.

¹H NMR (300 MHz, CDCl₃) δ 8.41 (s, 3H, NH3), 7.50 (d, 2H, Ar—H, ²J=8.0Hz), 7.32 (q, 3H, Ar—H, ²J=7.3 Hz), 7.22 (d, 2H, Ar—H, ²J=7.1 Hz), 7.12(d, 2H, Ar—H, ²J=7.9 Hz), 4.29 (t, 1H, NH3-CH, ²J=6.9 Hz), 4.02 (t, 2H,COO—CH2, ²J=6.4 Hz), 3.09 (AB spin sytem, 2H, NH3-CH—CH2, ²J=21.7 Hz),2.96 (t, 2H, CBr3-CH2, ²J=7.8 Hz), 2.29 (s, 3H, Ar—CH3), 1.68 (quin, 2H,COO—CH2-CH2, ²J=7.4 Hz), 1.50-1.08 (m, 16H, CH2). ¹³C NMR (101 MHz,CDCl₃) δ 169.02, 141.64, 140.35, 134.43, 129.56, 128.92, 128.70, 127.37,126.30, 66.37, 60.06, 54.33, 42.77, 36.51, 29.65, 29.57, 29.45, 29.31,28.21, 28.01, 25.72, 21.48. HRMS (ESI, m/z) 570.0044 [M]⁺, 570.0035calculated for C₂₁H₃₃Br₃NO₂.

12-Trichlorododecyl (S)-Phenylalaninate Ammonium Tosylate Salt

Preparation was achieved following the preliminary step as definedabove, using 12-trichlorododecanol and (S)-phenylalanine. 617 mg (76%)of product were obtained as a white powder.

¹H NMR (300 MHz, CDCl₃) δ 8.22 (s, 3H, NH3), 7.74 (d, 2H, Ar—H, ²J=8.2Hz), 7.21-7.07 (m, 7H, Ar—H), 4.35-4.20 (m, 1H, NH3-CH), 3.98-3.82 (m,2H, COO—CH2), 3.17 (AB spin sytem, 2H, NH3-CH—CH2, ²J=5.9 Hz), 2.67 (t,2H, CC13-CH2, ²J=8.0 Hz), 2.34 (s, 3H, Ar—CH3), 1.78 (quin, 2H,COO—CH2-CH2, ²J=7.4 Hz), 1.48-1.00 (m, 16H, CH2).¹³C NMR (101 MHz,CDCl₃) δ 169.00, 141.62, 140.40, 134.46, 129.57, 128.94, 128.70, 127.37,126.32, 66.37, 55.34, 54.35, 36.53, 29.65, 29.56, 29.44, 29.32, 28.48,28.22, 26.53, 25.73, 21.47. HRMS (ESI, m/z) 436.1575 [M]⁺, 436.1571calculated for C₂₁H₃₃Cl₃NO₂.

Example 3 Symmetric Ester Bis-Ureas with Linear Alkyl Chains

3.1. Bis-Ureas Synthetized from Phenylalanine (Phe)

H3C5Tol

Preparation was achieved following the method A using hexyl(S)-phenylalaninate ammonium tosylate salt. The product isrecrystallized in acetonitrile. 726 mg (85%) of a pure product wereobtained as a white paste.

¹H NMR (400 MHz, DMSO-d₆) δ 8.60 (s, 1H, NH), 7.81 (s, 1H, NH), 7.73 (d,1H, ArH, J=2.2 Hz), 7.35-7.17 (m, 11H, ArH), 7.11 (dd, 1H, ArH, J=8.2,2.2 Hz), 6.94 (d, 2H, NH, J=8.0 Hz), 6.28 (d, 1H, ArH, J=7.9 Hz),4.58-4.45 (m, 2H, NH—CH), 4.02 (t, 4H, COO—CH2, J=6.5 Hz), 3.09-2.93 (m,4H, NH3-CH—CH2), 2.08 (s, 3H, Ar—CH3), 1.58-1.45 (m, 4H, CH2), 1.31-1.17(m, 13H, CH2), 0.84 (t, 6H, CH3, J=6.8 Hz). ¹³C NMR (101 MHz, DMSO-d₆) δ172.20, 154.63, 154.48, 138.10, 137.80, 136.85, 136.78, 129.94, 129.13,128.26, 126.58, 119.48, 111.64, 110.01, 64.46, 53.97, 53.73, 37.72,37.56, 30.83, 27.99, 24.95, 21.94, 17.18, 13.82.

H3C6Tol

Preparation was achieved following the method A using heptyl(S)-phenylalaninate ammonium tosylate salt. The product isrecrystallized in acetonitrile. 823 mg (88%) of a pure product wereobtained as a white paste.

¹H NMR (400 MHz, DMSO-d₆/THF-d₈ 2/1) δ 8.60 (s, 1H, NH), 7.81 (s, 1H,NH), 7.77 (s, 1H, ArH), 7.34-7.15 (m, 13H, ArH), 6.96 (d, 1H, NH, J=7.8Hz), 6.90 (d, 1H, NH, J=8.3 Hz), 6.28 (d, 1H, ArH, J=8.0 Hz), 4.57 (h,2H, NH—CH, J=7.0 Hz), 4.04 (t, 4H, COO—CH2, J=6.7 Hz), 3.12-2.92 (m, 4H,NH3-CH—CH2), 2.11 (s, 3H, Ar—CH3), 1.62-1.48 (m, 4H, CH2), 1.26 (s, 16H,CH2), 0.87 (t, 6H, CH3, J=6.5 Hz). ¹³C NMR (101 MHz, DMSO-d₆/THF-d₈ 2/1)δ 172.10, 154.58, 154.44, 138.39, 137.97, 136.96, 129.65, 129.10,128.06, 126.37, 118.98, 114.60, 111.35, 109.69, 64.36, 53.95, 53.72,38.04, 37.87, 31.43, 25.45, 22.18, 17.03, 13.58. HRMS (ESI, m/z)723.4100 [M+Na]⁺, 723.4092 calculated for C₄₆H₅₆N₄O₆Na.

H3C7Tol

Preparation was achieved following the method A using heptyl(S)-phenylalaninate ammonium tosylate salt. The product isrecrystallized in acetonitrile.

HRMS (ESI, m/z) 751.4405 [M+Na]⁺, 751.4405 calculated for C₄₃H₆₀N₄O₆Na

H3C7Xyl

Preparation was achieved following the method B using octyl(S)-phenylalaninate ammonium tosylate salt and4,6-dimethyl-1,3-diaminobenzen. The product is recrystallized inacetonitrile. 963 mg (61%) of a pure product were obtained as a whitepaste.

¹H NMR (300 MHz, DMSO-d₆) δ 7.94 (s, 1H, ArH), 7.75 (s, 2H, NH),7.36-7.15 (m, 10H, ArH and NH), 6.85 (s, 1H, ArH), 6.69 (d, 2H, ArH,²J=7.9 Hz), 4.49 (q, 2H, NH—CH, ²J=7.2 Hz), 4.00 (t, 4H, COO—CH2, ²J=6.5Hz), 3.08-2.91 (m, NH3-CH—CH2, 4H), 2.05 (s, 6H, Ar—CH3), 1.50 (q, 4H,COOCHC2CH2, ²J=6.0 Hz), 1.30-1.15 (m, 20H, CH2), 0.85 (t, 6H, CH3,²J=6.7 Hz). ¹³C NMR (101 MHz, DMSO-d₆) δ 172.27, 154.73, 136.87, 135.27,131.20, 129.12, 128.22, 126.53, 122.40, 115.64, 64.42, 53.91, 37.74,31.20, 28.59, 28.54, 28.01, 25.27, 22.06, 17.17, 13.90. HRMS (ESI, m/z)765.4570 [M+Na]⁺, 765.4562 calculated for C₄₄H₆₂N₄O₆Na.

H3C7Cl

Preparation was achieved following the method B using octyl(S)-phenylalaninate ammonium tosylate salt and4,6-dichloro-1,3-diaminobenzene. The product is recrystallized inacetonitrile. 457 mg (55%) of pure product were obtained as a whitepowder.

¹H NMR (400 MHz, DMSO-d₆) δ 8.91 (s, 1H, ArH), 8.21 (s, 2H, NH), 7.46(s, 1H, ArH), 7.41 (d, 2H, J=7.7 Hz, ArH), 7.34-7.17 (m, 12H, ArH andNH), 4.49 (q, 2H, NH—CH, J=7.7 Hz), 4.01 (t, 4H, COO—CH2, J=6.2 Hz),3.08-2.91 (m, 4H NH3-CH—CH2), 1.55-1.42 (m, 4H, CH2), 1.30-1.13 (m, 20H,CH2), 0.83 (t, 6H, CH3, J=6.8 Hz). ¹³C NMR (101 MHz, DMSO-d₆) δ 172.00,153.90, 136.74, 135.43, 129.07, 128.28, 126.61, 114.37, 112.83, 64.52,54.01, 37.48, 31.19, 28.59, 28.55, 28.00, 25.28, 22.06, 13.89. HRMS(ESI, m/z) 805.3468 [M+Na]⁺, 805.3469 calculated for C₄₂H₅₆Br₄Cl₂N₄O₆Na.

H3C8Tol

Preparation was achieved following the method A using nonyl(S)-phenylalaninate ammonium tosylate salt. The product isrecrystallized in acetonitrile. 1.42 g (83%) of a pure product wereobtained as a white paste.

¹H NMR (300 MHz, DMSO-d₆) δ 8.58 (s, 1H, ArH), 7.75 (d, 2H, NH, ²J=30.5Hz), 7.35-7.15 (m, 10H, ArH), 7.10 (d, 1H, NH, ²J=8.3 Hz), 6.92 (d, 2H,ArH, ²J=7.9 Hz), 6.26 (d, 1H, NH, ²J=7.9 Hz), 4.49 (p, 2H, NH—CH, ²J=7.3Hz), 4.01 (t, 4H, COO—CH2, ²J=6.4 Hz), 3.06-2.92 (m, 4H, NH3-CH—CH2),2.07 (s, 3H, Ar—CH3), 1.55-1.44 (m, 4H, COO—CH2-CH2), 1.30-1.15 (m, 24H,CH2), 0.85 (t, 3H, CH3, ²J=6.9 Hz). ¹³C NMR (101 MHz, DMSO-d₆) δ 172.18,154.61, 154.46, 138.07, 137.78, 136.84, 136.78, 129.93, 129.11, 128.25,126.57, 119.41, 111.58, 109.94, 64.44, 53.96, 53.73, 37.68, 37.52,31.24, 28.84, 28.62, 28.01, 25.27, 22.06, 17.18, 13.91. HRMS (ESI, m/z)779.4716 [M+Na]⁺, 779.4718 calculated for C₄₅H₆₄N₄O₆Na.

H3C8Xyl

Preparation was achieved following the method B using nonyl(S)-phenylalaninate ammonium tosylate salt and4,6-dimethyl-1,3-diaminobenzene. The product is recrystallized inacetonitrile. 465 mg (59%) of a pure product were obtained as a whitepaste.

¹H NMR (300 MHz, DMSO-d₆) δ 7.94 (s, 1H, ArH), 7.75 (s, 2H, NH),7.36-7.15 (m, 10H, ArH and NH), 6.85 (s, 1H, ArH), 6.69 (d, 2H, ArH,²J=7.9 Hz), 4.49 (q, 2H, NH—CH, ²J=7.2 Hz), 4.00 (t, 4H, COO—CH2, ²J=6.5Hz), 3.08-2.91 (m, NH3-CH—CH2, 4H), 2.05 (s, 6H, Ar—CH3), 1.50 (q, 4H,COOCHC2CH2, ²J=6.0 Hz), 1.30-1.15 (m, 24H, CH2), 0.85 (t, 6H, COO—CH2,²J=6.7 Hz). ¹³C NMR (101 MHz, DMSO-d₆) δ 172.27, 154.73, 136.87, 135.26,131.19, 129.11, 128.22, 126.52, 122.38, 64.41, 53.90, 37.73, 31.25,28.62, 28.00, 25.26, 22.07, 17.17, 13.91. HRMS (ESI, m/z) 793.4886[M+Na]⁺, 793.4875 calculated for C₄₆H₆₆N₄O₆Na.

H3C9Tol

Preparation was achieved following the method A using decyl(S)-phenylalaninate ammonium tosylate salt. The product isrecrystallized in acetonitrile. 1.42 g (83%) of a pure product wereobtained as a white paste.

¹H NMR (400 MHz, DMSO-d₆) δ 8.60 (s, 1H, ArH), 7.78 (d, 2H, NH, ²J=28.8Hz), 7.42-7.12 (m, 10H, ArH), 7.12 (d, 1H, NH, ²J=6.9 Hz), 6.94 (d, 2H,ArH, ²J=5.1 Hz), 6.28 (d, 1H, NH, ²J=6.7 Hz), 4.59-4.44 (m, 2H, NH—CH),4.02 (t, 4H, COO—CH2, ²J=6.4 Hz), 3.06-2.92 (m, 4H, NH3-CH—CH2), 2.09(s, 3H, Ar—CH3), 1.58-1.45 (m, 4H, COO—CH2-CH2), 1.30-1.15 (m, 28H,CH2), 0.86 (t, 3H, CH3, ²J=6.9 Hz). ¹³C NMR (101 MHz, DMSO-d₆) δ 172.17,154.61, 154.46, 138.09, 137.79, 136.84, 136.78, 129.91, 129.11, 128.23,126.55, 119.38, 111.58, 109.94, 64.44, 53.96, 53.73, 37.71, 37.55,31.28, 28.93, 28.92, 28.90, 28.69, 28.64, 28.02, 25.28, 22.09, 17.18,13.90. HRMS (ESI, m/z) 807.5029 [M+Na]⁺, 807.5031 calculated forC₄₇H₈₈N₄O₆Na.

H3C10Tol

Preparation was achieved following the method A using undecyl(S)-phenylalaninate ammonium tosylate salt. The product isrecrystallized in acetonitrile. 1.82 g (99%) of a pure product wereobtained as a white paste.

¹H NMR (400 MHz, DMSO-d₆) δ 8.60 (s, 1H, ArH), 7.78 (d, 2H, NH, ²J=27.5Hz), 7.37-7.14 (m, 10H, ArH), 7.12 (d, 1H, NH, ²J=6.7 Hz), 6.94 (d, 2H,ArH, ²J=5.1 Hz), 6.28 (d, 1H, NH, ²J=6.0 Hz), 4.59-4.44 (m, 2H, NH—CH),4.02 (t, 4H, COO—CH2, ²J=6.4 Hz), 3.06-2.92 (m, 4H, NH3-CH—CH2), 2.09(s, 3H, Ar—CH3), 1.58-1.45 (m, 4H, COO—CH2-CH2), 1.30-1.15 (m, 32H,CH2), 0.86 (t, 3H, CH3, ²J=6.9 Hz). ¹³C NMR (101 MHz, DMSO-d₆) δ 172.16,154.45, 138.10, 137.79, 136.84, 136.77, 129.90, 129.10, 128.22, 126.54,119.36, 111.58, 109.94, 64.43, 53.95, 53.72, 37.71, 37.56, 31.29, 28.99,28.90, 28.71, 28.65, 28.02, 25.29, 22.09, 17.18, 13.89.

H3C11Xyl

Preparation was achieved following the method B using dodecyl(S)-phenylalaninate ammonium tosylate salt and4,6-dimethyl-1,3-diaminobenzene. The product is recrystallized twice inacetonitrile. 1.49 g (62%) of a pure product were obtained as a whitepaste.

¹H NMR (300 MHz, DMSO-d₆/THF-d₈ 2/1) δ 7.95 (s, 1H, ArH), 7.75 (s, 2H,NH), 7.36-7.15 (m, 10H, ArH and NH), 6.85 (s, 1H, ArH), 6.70 (d, 2H,ArH, ²J=7.6 Hz), 4.49 (q, 2H, NH—CH, ²J=6.7 Hz), 4.00 (t, 4H, COO—CH2,²J=6.2 Hz), 3.08-2.91 (m, NH3-CH—CH2, 4H),), 2.05 (s, 6H, Ar—CH3), 1.50(q, 4H, COOCHC2CH2, ²J=6.0 Hz), 1.30-1.15 (m, 36H, CH2), 0.85 (t, 6H,COO—CH2, ²J=6.7 Hz). ¹³C NMR (101 MHz, DMSO-d₆/THF-d₈ 2/1) δ 173.59,156.09, 138.36, 136.86, 132.38, 130.49, 129.43, 127.72, 123.84, 117.23,65.74, 55.28, 39.42, 32.81, 30.56, 30.53, 30.51, 30.43, 30.24, 30.19,29.52, 26.81, 25.65, 25.45, 25.25, 25.05, 23.56, 18.43, 14.99. HRMS(ESI, m/z) 877.5807 [M+Na]⁺, 877.5814 calculated for C₅₂H₇₈N₄O₆Na.

H3C12Tol

Preparation was achieved following the method A using tridecyl(S)-phenylalaninate ammonium tosylate salt. The product isrecrystallized in acetonitrile. 757 mg (99%) of a pure product wereobtained as a white paste.

¹H NMR (400 MHz, DMSO-d₆) δ 8.58 (s, 1H, ArH), 7.79 (s, 1H, NH), 7.73(s, 1H, NH), 7.35-7.14 (m, 11H, ArH), 7.09 (d, 2H, ArH, J=7.6 Hz), 6.92(d, 2H, NH, J=8.2 Hz), 6.26 (d, 1H, ArH, J=7.9 Hz), 4.56-4.43 (m, 2H,NH—CH), 4.00 (t, 4H, COO—CH2, J=6.5 Hz), 2.99 (q, 4H, NH3-CH—CH2, J=7.3,6.4 Hz), 2.07 (s, 3H, Ar—CH3), 1.58-1.41 (m, 4H, CH2), 1.36-1.07 (m,36H, CH2), 0.85 (t, 6H, CH3, J=6.6 Hz). ¹³C NMR (101 MHz, DMSO-d₆) δ172.16, 154.60, 138.09, 137.78, 136.84, 136.77, 129.90, 129.10, 128.22,126.54, 119.37, 111.58, 109.95, 64.42, 53.96, 53.73, 37.69, 37.54,31.29, 29.05, 29.02, 28.97, 28.89, 28.71, 28.64, 28.02, 25.28, 22.08,17.18, 13.89. HRMS (ESI, m/z) 891.5964 [M+Na]⁺, 891.5970 calculated forC₅₃H₈₀N₄O₆Na.

H3C13Tol

Preparation was achieved following the method A using tetradecyl(S)-phenylalaninate ammonium tosylate salt. The product isrecrystallized in acetonitrile. 746 mg (96%) of a pure product wereobtained as a white paste.

¹H NMR (400 MHz, DMSO-d₆/THF-d8 2/1) δ 8.60 (s, 1H, ArH), 7.79 (d, 2H,NH, J=16.7 Hz), 7.38-7.15 (m, 10H, ArH), 6.96 (d, 1H, ArH, J=7.8 Hz),6.90 (d, 1H, ArH, J=8.3 Hz), 6.28 (d, 1H, NH, J=8.0 Hz), 4.57 (dd, 2H,NH—CH, J=14.9, 7.4 Hz), 4.03 (t, 4H, COO—CH2, J=6.7 Hz), 3.12-2.94 (m,4H, NH3-CH—CH2), 2.11 (s, 3H, Ar—CH3), 1.64-1.46 (m, 4H, CH2), 1.43-1.06(m, 40H, CH2), 0.87 (t, 6H, CH3, J=6.5 Hz). ¹³C NMR (101 MHz,DMSO-d₆/THF-d8 2/1) δ 172.11, 154.58, 154.45, 138.39, 137.97, 136.96,136.90, 129.66, 129.10, 128.07, 126.37, 118.99, 114.60, 111.37, 109.69,64.38, 53.94, 53.72, 38.04, 37.86, 31.43, 31.43, 29.19, 29.06, 28.85,28.16, 25.44, 22.18, 22.18, 17.04, 13.59. HRMS (ESI, m/z) 919.6298[M+Na]⁺, 919.6283 calculated for C₅₅H₈₄N₄O₆Na.

H3C15Tol

Preparation was achieved following the method A using hexadecyl(S)-phenylalaninate ammonium tosylate salt. The product isrecrystallized in acetonitrile. 2.01 g (93%) of a pure product wereobtained as a white paste.

¹H NMR (400 MHz, DMSO-d₆) δ 8.59 (s, 1H, NH), 7.81 (s, 1H, NH), 7.77 (d,1H, ArH, J=2.2 Hz), 7.33-7.26 (m, 4H, ArH), 7.26-7.17 (m, 7H, ArH), 6.96(d, 1H, ArH, J=7.8 Hz), 6.90 (d, 1H, NH, J=8.3 Hz), 6.27 (d, 1H, NH,J=7.9 Hz), 4.63-4.47 (m, 2H, NH—CH), 4.03 (t, 4H, COO—CH2, J=6.7 Hz),3.11-2.94 (m, 4H, NH3-CH—CH2), 2.10 (s, 3H, Ar—CH3), 1.60-1.48 (m, 4H,CH2), 1.37-1.18 (m, 52H, CH2), 0.87 (t, 6H, CH3, J=6.7 Hz). ¹³C NMR (101MHz, DMSO-d₆) δ 172.00, 154.48, 154.34, 138.25, 137.85, 136.84, 136.78,129.57, 128.99, 127.98, 126.28, 118.93, 111.29, 109.62, 66.30, 66.08,65.87, 65.65, 64.28, 53.84, 53.62, 37.90, 37.72, 31.31, 29.07, 29.03,28.94, 28.73, 28.04, 25.32, 24.17, 23.97, 23.77, 22.07, 16.94, 13.51.HRMS (ESI, m/z) 835.5340 [M+Na]⁺, 853.5344 calculated for C₄₉H₇₂N₄O₆Na.

H3C15Xyl

Preparation was achieved following the method B using hexadecyl(S)-phenylalaninate ammonium tosylate salt and4,6-dimethyl-1,3-diaminobenzene. The product is recrystallized twice inacetonitrile. 1.05 g (64%) of a pure product were obtained as a whitepaste.

¹H NMR (400 MHz, DMSO-d₆/THF-d8 2/1) δ 8.02 (s, 1H, ArH), 7.77 (s, 2H,NH), 7.33-7.15 (m, 12H, ArH), 6.83 (s, 1H, ArH), 6.71 (d, 2H, NH, J=8.0Hz), 4.57 (q, 2H, NH—CH, J=7.0 Hz), 4.02 (t, 4H, COO—CH2, J=6.5 Hz),3.02 (dd, NH3-CH—CH2, 4H, J=6.6, 3.3 Hz), 2.08 (s, 6H, Ar—CH3),1.60-1.45 (m, 4H, CH2), 1.39-1.13 (m, 62H, CH2), 0.87 (t, H, CH3, J=6.7Hz). ¹³C NMR (101 MHz, DMSO-d₆/THF-d8 2/1) δ 172.11, 154.61, 136.88,135.36, 130.90, 129.01, 127.95, 126.24, 122.33, 115.73, 64.25, 53.80,31.31, 29.07, 29.03, 28.94, 28.73, 28.70, 28.03, 25.32, 22.07, 16.95,13.51. HRMS (ESI, m/z) 989.7085 [M+Na]⁺, 989.7066 calculated forC₆₀H₉₄N₄O₆Na.

H3C17Tol

Preparation was achieved following the method A using octodecyl(S)-phenylalaninate ammonium tosylate salt. The product isrecrystallized in acetonitrile. 923 mg (92%) of a pure product wereobtained as a white paste. The S enantiomer was synthesized as well (88%yield).

¹H NMR (400 MHz, DMSO-d₆/THF-d8 2/1) δ 8.60 (s, 1H, NH), 7.82 (s, 1H,NH), 7.77 (d, 1H, ArH, J=2.2 Hz), 7.34-7.17 (m, 12H, ArH), 6.97 (d, 1H,NH, J=7.9 Hz), 6.90 (d, 1H, NH, J=8.3 Hz), 6.29 (d, 1H, ArH, J=8.0 Hz),4.64-4.48 (m, 2H, NH—CH), 4.09-3.98 (m, 4H, COO—CH2), 3.12-2.95 (m, 4H,NH3-CH—CH2), 2.20-2.05 (m, 3H, Ar—CH3), 1.54 (p, 4H, CH2, J=6.5 Hz),1.36-1.17 (m, 60H, CH2), 0.87 (t, 6H, CH3, J=6.7 Hz). ¹³C NMR (101 MHz,DMSO-d₆/THF-d8 2/1) δ 172.10, 154.59, 154.44, 138.40, 137.98, 136.97,136.91, 129.64, 129.10, 128.05, 126.36, 118.98, 111.37, 109.70, 64.36,53.95, 53.73, 38.05, 37.87, 31.44, 29.20, 29.16, 29.08, 28.86, 28.17,25.46, 25.44, 22.19.

H3C7d₅-PheTol

Preparation was achieved following the method A using octyl(S)-d₅-phenylalaninate ammonium tosylate salt. The product isrecrystallized in acetonitrile. 649 mg (73%) of a pure product wereobtained as a white paste.

¹H NMR (300 MHz, DMSO-d₆) δ 8.59 (s, 1H, NH), 7.80 (s, 1H, ArH), 7.72(s, 1H, NH), 7.10 (d, 1H, NH, ²J=8.3 Hz), 6.93 (d, 2H, ArH, ²J=7.4 Hz),6.27 (d, 1H, NH, ²J=8.1 Hz), 4.49 (qi, 2H, NH—CH, ²J=7.2 Hz), 4.01 (t,4H, COO—CH2, ²J=6.5 Hz), 3.05-2.95 (m, 4H, COO—CH2-CH2), 2.07 (s, 3H,Ar—CH3), 1.56-1.44 (m, 4H, COO—CH2-CH2-CH2), 1.33-1.15 (m, 44H, CH2),0.84 (t, 3H, CH3, ²J=6.5 Hz). ¹³C NMR (101 MHz, DMSO-d₆) δ 172.20,154.62, 154.48, 138.10, 137.79, 136.66, 136.59, 129.93, 119.43, 111.61,109.97, 64.45, 53.96, 53.74, 37.60, 37.44, 31.20, 28.60, 28.55, 28.02,25.28, 22.06, 17.18, 13.89. HRMS (ESI, m/z) 761.5039 [M+Na]⁺, 761.5033calculated for C₃₅H₅₀D₁₀N₄O₆Na.

3.2. Halogen Functionalized Ester Bis-Ureas

Br3C11Tol

Preparation was achieved following the method A using 12-tribromododecyl(S)-phenylalaninate ammonium tosylate salt. The product isrecrystallized in acetonitrile. 2.04 g (84%) of a pure product wereobtained as a white paste.

¹H NMR (300 MHz, DMSO-d₆) δ 8.59 (s, 1H, NH), 7.80 (s, 1H, NH), 7.72 (d,1H, ArH, ²J=1.7 Hz), 7.36-7.02 (m, 11H, ArH and NH), 6.93 (d, 2H, ArH,²J=8.2 Hz), 6.27 (d, 2H, ArH, ²J=7.7 Hz), 4.48 (p, 2H, NH—CH, ²J=7.0Hz), 4.01 (t, 4H, COO—CH2, ²J=6.3 Hz), 3.06-2.90 (m, 8H, NH3-CH—CH2 andCBr3-CH2), 2.07 (s, 3H, Ar—CH3), 1.67 (p, 4H, COO—CH2-CH2, ²J=7.5 Hz),1.59-1.45 (m, 4H, ArO-CH2-CH2), 1.45-1.15 (m, 28H, CH2). ¹³C NMR (101MHz, DMSO-d₆) δ 172.17, 154.60, 138.08, 137.78, 136.84, 136.77, 129.93,129.12, 128.25, 126.57, 119.38, 111.58, 109.92, 64.45, 58.68, 53.72,43.37, 37.69, 37.54, 29.16, 28.86, 28.74, 28.62, 28.02, 27.08, 25.27,17.22. HRMS (ESI, m/z) 1335.0275 [M+Na]⁺, 1335.0247 calculated forC₅₁H₇₀Br₆N₄O₆Na.

Br3C11Xyl

Preparation was achieved following the method B using 12-tribromododecyl(S)-phenylalaninate ammonium tosylate salt and4,6-dimethyl-1,3-diaminobenzene. The product is recrystallized inacetonitrile. 707 mg (28%) of a pure product were obtained as a whitepaste.

¹H NMR (300 MHz, DMSO-d₆) δ 7.95 (s, 1H, ArH), 7.75 (s, 2H, NH),7.35-7.15 (m, 13H, ArH and NH), 6.98-6.80 (m, 8H, ArH and NH), 6.85 (s,1H, ArH), 6.70 (d, 2H, ArH, ²J=7.8 Hz), 4.49 (q, 2H, NH—CH, ²J=7.2 Hz),4.00 (t, 4H, COO—CH2, ²J=6.4 Hz), 3.05-2.90 (m, CBr3-CH2 and NH3-CH—CH2,8H), 2.05 (s, 6H, Ar—CH3), 1.67 (p, 4H, COO—CH2-CH2, ²J=7.3 Hz),1.58-1.15 (m, 32H, CH2). ¹³C NMR (101 MHz, DMSO-d₆) δ 172.26, 154.71,144.47, 137.61, 136.86, 135.25, 131.18, 129.11, 128.22, 126.53, 122.38,64.42, 58.65, 53.90, 43.37, 37.72, 29.15, 28.83, 28.71, 28.60, 28.00,27.06, 25.25, 17.18. HRMS (ESI, m/z) 1349.0413 [M+Na]⁺, 1349.0403calculated for C₅₂H₇₂Br₆N₄O₆Na.

Br3C11Cl

Preparation was achieved following the method B using 12-tribromododecyl(S)-phenylalaninate ammonium tosylate salt and4,6-dichloro-1,3-diaminobenzene. The product is recrystallized inacetonitrile. 1.09 g (68%) of pure product were obtained as a whitepowder.

¹H NMR (300 MHz, DMSO-d₆) δ 8.91 (s, 1H, ArH), 8.19 (s, 2H, NH),7.50-7.12 (m, 13H, ArH and NH), 4.57-4.42 (m, 2H, NH—CH), 4.00 (t, 4H,COO—CH2, ²J=4.7 Hz), 2.97 (m, NH3-CH—CH2 and CBr3-CH2, 8H), 1.78-1.58(m, 4H, COO—CH2-CH2), 1.65-1.10 (m, 32H, CH2). ¹³C NMR (101 MHz,DMSO-d₆) δ 171.97, 153.86, 136.72, 135.42, 129.05, 128.26, 128.13,126.59, 114.30, 112.77, 64.50, 58.67, 53.98, 43.36, 37.48, 29.15, 28.85,28.73, 28.61, 27.99, 27.08, 25.27. HRMS (ESI, m/z) 1388.9324 [M+Na]⁺,1388.9311 calculated for C₅₀H₆₆Br₆Cl₂N₄O₆Na.

C13C11Xyl

Preparation was achieved following the method B using12-trichlorododecyl (S)-phenylalaninate ammonium tosylate salt and4,6-dimethyl-1,3-diaminobenzene. The product is recrystallized inacetonitrile. 291 mg (64%) of a pure product were obtained as a whitepaste.

¹H NMR (300 MHz, DMSO-d₆) δ 7.95 (s, 1H, ArH), 7.75 (s, 2H, NH),7.35-7.15 (m, 15H, ArH and NH), 6.98-6.80 (m, 8H, ArH and NH), 6.85 (s,1H, ArH), 6.70 (d, 2H, ArH, ²J=7.8 Hz), 4.49 (q, 2H, NH—CH, ²J=7.2 Hz),4.00 (t, 4H, COO—CH2, ²J=6.4 Hz), 3.04-2.94 (m, NH3-CH—CH2, 4H), 2.72(t, CC13-CH2, ²J=7.9 Hz), 2.05 (s, 6H, Ar—CH3), 1.67 (p, 4H,COO—CH2-CH2, ²J=7.3 Hz), 1.58-1.15 (m, 32H, CH2). ¹³C NMR (75 MHz,DMSO-d₆) δ 172.76, 155.22, 137.37, 135.77, 131.69, 129.61, 128.72,127.02, 122.89, 116.16, 101.03, 64.92, 54.62, 54.41, 38.25, 29.34,29.31, 29.17, 29.11, 28.51, 27.98, 26.59, 25.77, 17.68. HRMS (ESI, m/z)1083.3474 [M+Na]⁺, 1083.3446 calculated for C₅₂H₇₂Cl₆N₄O₆Na.

Part 2: Physico-Rheological Tests

Example 4 Effect of Temperature on Relative Viscosity

The aim of this experiment was to measure the effect of the temperatureon the evolution of the relative viscosity of non-polar liquids.

Viscosity is a measure of a fluid's resistance to flow. In thisexperiment, the relative viscosity has been evaluated by measuring theflow time of the sample at various temperatures using 0.1 mM solution ofH3C11Xyl either in methylcyclohexane or in dodecane.

The results (FIG. 2) show that:

-   -   for the liquids only—i.e. free of H3C11Xyl—(dodecane or        methylcyclohexane), the flow time dramatically decreases when        the temperature increases until 120° C.;    -   when H3C11Xyl is added to either dodecane or methylcyclohexane        (non-polar liquid), the flow time is higher than the one of the        corresponding solution without the compound of invention;    -   in the temperature range from about 20° C. to 45° C. for the        solution of H3C11Xyl in dodecane or in the range from about        22° C. to 55° C. for the solution of H3C11Xyl in        methylcyclohexane, the flow time of solutions comprising        H3C11Xyl does not decrease, and even slightly increases, when        the temperature rises.

In conclusion, these experiments evidence that the compound of theinvention (ester bis-ureas) acts as a thermo-thickening agent when addedin a non-polar liquid such as dodecane or methylcycloxane.

Example 5 Influence of Alkyl Chain Length

The aim of this experiment is to investigate the influence of the lengthof the alkyl chain on the evolution of the relative viscosity bycomparing an ester bis-urea with an octyl chain, a dodecyl chain and ahexadecyl chain.

This experiment is carried out by solubilizing in a non-polar liquid ata concentration of 0.1 mM: H3C7Xyl (ester bis-urea with octyl chain),H3C11Xyl (ester bis-urea with dodecyl chain) or H3C15Xyl (ester bis-ureawith hexadecyl chain), as described above. The non-polar liquids arechosen among methylcyclohexane and dodecane.

The results (FIG. 3) show that for all solutions comprising an esterbis-ureas with octyl (H3C7Xyl), dodecyl (H3C11Xyl) or hexadecyl(H3C15Xyl) chain, the relative viscosity increases or is maintained whensolutions are heated from 5° C. to about 70° C.

In conclusion, these experiments evidence that ester bis-ureas with longalkyl chains act as efficient thermo-thickening agent when added in anon-polar liquid heated at a temperature ranging from about 5° C. to 70°C.

Example 6 Rheology Test

The aim of this experiment is to show the rheology behavior of acomposition of the invention.

For this purpose, the storage modulus (G′—elastic response) and the lossmodulus (G″—viscous behavior) have been measured at 1 rad/s, for asolution of H3C11Xyl in dodecane (4.1 g/L). G′ and G″ allow havinginformation regarding the complex viscosity of a sample.

The results (FIGS. 4 and 5) show that the complex viscosity increases by1.5 for a solution comprising a compound of the invention heated at atemperature ranging from 20° C. to 50° C.

1-15. (canceled)
 16. A method for thermo-thickening a compositioncomprising the addition to said composition of a compound of generalformula (IV):

wherein: R_(a), R_(b), R_(c) and R_(d) are each independently selectedfrom H, alkyl, heteroalkyl, alkoxy, amino, alkylamino and halo; R₁′ andR₂′ are each independently selected from linear alkyl, heteroalkyl,alkenyl, heteroalkenyl, alkynyl, heteroalkynyl and macromoleculargroups, substituted or not substituted by one or more halo; R₃′, R₃, R₄,R₄′ R₅, R₅′, R₆ and R₆′ are each independently selected from H, alkyl,alkenyl, aryl, heteroalkyl, heteroalkenyl, heteroaryl, alkylaryl,arylalkyl, heteroarylalkyl or alkylheteroaryl, substituted or notsubstituted by guanidine, aryl, pyrrolidine, imidazole, hydroxyaryl,carboxy, selanyl, hydroxyl, amide, thiol, alkylthio, amino, deuterium orhalo; Z₁ and Z₁′ are each independently selected from O and S atoms; Z₂and Z₂′ are each independently selected from —NH—, O and S atoms; nrepresents a positive integer from 0 to 10; and optionally, * stands fora stereogenic center; provided that R₁′ and R₂′ does not represent botha methyl group.
 17. The method according to claim 16, wherein thecompound is of general formula (IV bis):

wherein R_(a), R_(b), R_(c), R_(d), R₁′, R₂′, R₃, R₃′, R₄, R₄′, Z₁, Z₁′,Z₂ and Z₂′ are as defined in claim
 16. 18. The method according to claim17, wherein in the compound of formula (IVbis), R_(a) and R_(c) are bothH.
 19. The method according to claim 16, wherein said composition is anon-polar liquid.
 20. The method according to claim 16, whereinthermo-thickening is performed at a temperature ranging from 5° C. to100° C.
 21. The method according to claim 16, for further improving thecold flow property of a non-polar liquid.
 22. A Compound of generalformula (IV):

wherein: R_(a), R_(b), R_(c) and R_(d) are each independently selectedfrom H, alkyl, heteroalkyl, alkoxy, amino, alkylamino and halo; R₁′ andR₂′ are each independently selected from linear alkyl, heteroalkyl,alkenyl, heteroalkenyl, alkynyl, heteroalkynyl and macromoleculargroups, substituted or not substituted by one or more halo R₃′, R₃, R₄,R₄′ R₅′, R₅, R₆ and R₆′ are each independently selected from H, alkyl,alkenyl, aryl, heteroalkyl, heteroalkenyl, heteroaryl, alkylaryl,arylalkyl, heteroarylalkyl or alkylheteroaryl, substituted or notsubstituted by guanidine, aryl, pyrrolidine, imidazole, hydroxyaryl,carboxy, selanyl, hydroxyl, amide, thiol, alkylthio, amino, deuterium orhalo; Z₁ and Z₁′ are each independently selected from O and S atoms; Z₂and Z₂′ are each independently selected from —NH—, O and S atoms; nrepresents a positive integer from 0 to 10 and optionally, * stands fora stereogenic center; provided that R₁′ and R₂′ does not represent botha methyl group.
 23. The compound according to claim 22, wherein n isequal to 0 (i.e. compounds having formula (IV bis)).
 24. The compoundaccording to claim 23, wherein Z₁, Z₁′, Z₂ and Z₂′ represent O atoms.25. The compound according to claim 24, selected from: (2S,2′S)-dihexyl2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-diheptyl2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-dioctyl2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-dioctyl2,2′-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-dioctyl2,2′-((((4,6-dichloro-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-dinonyl2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-dinonyl2,2′-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-didecyl2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-diundecyl2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-didodecyl2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-didodecyl2,2′-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-ditridecyl2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-ditetradecyl2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-dihexadecyl2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-dihexadecyl2,2′-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-dioctadecyl2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-dioctyl2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-pentadeuteriumphenylpropanoate);(2S,2′S)-bis(12,12,12-tribromododecyl)2,2′-((((4-methyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-bis(12,12,12-tribromododecyl)2,2′-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);(2S,2′S)-bis(12,12,12-tribromododecyl)2,2′-((((4,6-dichloro-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate);and (2S,2′S)-bis(12,12,12-trichlorododecyl)2,2′-((((4,6-dimethyl-1,3-phenylene)bis(azanediyl))bis(carbonyl))bis(azanediyl))bis(3-phenylpropanoate).26. A composition comprising at least one compound of claim 22, and anon-polar liquid.
 27. The composition according to claim 26, wherein theliquid is selected from an oil (or lubricant), a grease, a monomer, athermosetting resin, a perfume or a fuel.
 28. The composition accordingto claim 26, wherein the compound is at a concentration ranging frommore than 0 to 5% by weight to the total weight of the composition. 29.A process for manufacturing a compound of formula (IV bis) according toclaim 23, comprising reacting at least one ester ammonium salt offormula (A-1):

wherein R₃′ and R₃ are each independently selected from H, alkyl,alkenyl, aryl, heteroalkyl, heteroalkenyl, heteroaryl, alkylaryl,arylalkyl, heteroarylalkyl or alkylheteroaryl, substituted or notsubstituted by guanidine, aryl, pyrrolidine, imidazole, hydroxyaryl,carboxy, selanyl, hydroxyl, amide, thiol, alkylthio, amino, deuterium orhalo; R₁′ is each independently selected from linear alkyl, heteroalkyl,alkenyl, heteroalkenyl, alkynyl and heteroalkynyl group, substituted ornot substituted by one or more halo; and X⁻ is an anion. with (a) eithera diisocyanate of general formula (A-2bis):

wherein R_(a), R_(b), R_(c) and R_(d) are each independently selectedfrom H, alkyl, heteroalkyl, alkoxy, amino, alkylamino and halo; (b) or amixture of reagents allowing the in situ preparation of diisocyanate offormula (A-2bis).
 30. The process according to claim 29, furthercomprising a preliminary step of preparing ester ammonium salt offormula (A-1) by reacting an amino acid and an alcohol such ashydroxyalkane.
 31. The method according to claim 16, wherein saidcomposition is selected from an oil, a grease, a monomer, athermosetting resin, a perfume or a fuel.
 32. The method according toclaim 16, wherein R_(b) and R_(d) are each independently selected fromH, C₁-C₄ alkyl, C₁-C₄ heteroalkyl, C₁-C₄ alkoxy, C₁-C₄ dialkylamino andhalo.
 33. The method according to claim 16, wherein R₁′ and R₂′ are eachindependently selected from linear alkyl or linear heteroalkyl group,said linear group being substituted or not substituted by one or morehalo.
 34. The method according to claim 16, wherein R₃′, R₃, R₄, R₄′,R₅′, R₅, R₆ and R₆′ are each independently selected from H, C₁-C₁₂ alkylsubstituted by at least one aryl, said aryl being substituted or notsubstituted by one or more halo or deuterium.
 35. The method accordingto claim 16, wherein n is equal to 0.